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Mind over Matter How Non-invasive Neuromodulation Is Becoming the Future of Pain Management by EOS Intelligence

08/10/2024by EOS Intelligence EOS Intelligence No Comments

Mind over Matter: How Non-invasive Neuromodulation Is Becoming the Future of Pain Management and Beyond

Scientists have been researching the possibility of using electrical impulses to treat many health conditions. The starting point was the introduction of the first TENS (transcutaneous electrical nerve stimulation) device in the 1970s in the USA. Its goal was to test the tolerance of chronic pain patients to electrical stimulation. In recent years, non-invasive neuromodulation has emerged as a promising field for treating various neurological disorders. This field will likely experience significant growth in the coming decade, thanks to technological advancements, such as AI-powered sophisticated wearables.

Non-invasive neuromodulation is emerging as a novel treatment for several diseases

Non-invasive neuromodulation is a technique that uses external devices to apply electromagnetic fields, electrical currents, or other forms of stimulation to the brain to enable targeted modulation of neural activity.

The technique is effective in treating a range of conditions. Currently, several devices are available in the market for treating illnesses, including chronic pain, tinnitus, diabetic neuropathy, and functional disorders such as bladder and bowel control.

The non-invasive neuromodulation market encompasses a diverse array of devices that can modify neural activity without the need for invasive procedures. This includes transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), and TENS.

TMS therapy sessions typically require the presence of a physician. An example is MagVenture Pain Therapy, a TMS device developed by a Denmark-based company, MagVenture, for treating chronic pain.

TENS and tDCS devices are portable and, hence, suitable for at-home treatments. The FDA has not yet approved tDCS in the USA for medical use. However, its use falls under the Investigational Device Exception (IDA) regulations. Though it is marketed for non-medical uses in the USA, it is used for medical treatment in regions such as the EU, Singapore, and Israel.

TENS devices are small, battery-powered devices that consist of leads that connect to electrodes, sticky pads placed on the skin in the area that needs stimulation. An example is Cefaly, an FDA-approved TENS device developed by the US-based Cefaly Technology for pain management. This device works by stimulating and desensitizing the primary source of migraine pain, the trigeminal nerve, using a precise electrical impulse.

Mind over Matter How Non-invasive Neuromodulation Is Becoming the Future by EOS Intelligence

The non-invasive neuromodulation market is showing rapid growth

The global non-invasive neuromodulation devices market for neurological and psychiatric disorders was approximately US$1.2 billion in 2022. According to a 2023 report by Report Prime, an India-based market research firm, the market is projected to grow at a CAGR of 7.2% from 2023 to 2030, reaching US$2.1 billion by 2030.

Several reasons fuel this rapid growth in recent years, including the increasing prevalence of chronic pain and other neurological conditions (especially in older patients), the numerous advantages this technique has over invasive neuromodulation, breakthroughs in non-invasive technology, and a surge in investments.

Increasing incidence of neurological disorders is a major driver

The increasing incidence of debilitating disorders such as chronic pain, Parkinson’s disease, diabetic neuropathy, etc., is creating a pressing need for new and efficient treatments to address these conditions. A 2023 study by the CDC indicated that 20.9% of American adults suffered from chronic pain, and 6.9% experienced chronic pain that significantly limited their daily activities.

Similarly, Parkinson’s disease affects nearly 1 million people in the USA as of 2023, with this number expected to rise to 1.2 million by 2030. These statistics indicate a rising trend of neurological disease burden in the USA.

One major issue that many patients and physicians face is that the current treatments for many of these conditions fall short, leaving a significant gap in the care of patients. Typically, doctors treat people suffering from chronic pain, including that of diabetic neuropathy, using painkillers. Most patients develop medicine tolerance, experience drug-wearing-off effects, or suffer from severe side effects, diminishing the overall treatment effectiveness.

Some patients may even consider drastic and irreversible surgical procedures, such as nerve amputation, due to inadequate treatment results. However, even these may not always provide the desired relief. This indicates the need for a reliable and effective solution for managing the pain, discomfort, and other neurological symptoms associated with the primary disease.

As non-invasive neuromodulation stimulates the brain areas responsible for pain processing, it alters the patient’s perception of pain. With the growing incidence of neurological disorders, this desired neuromodulation effect will continue to be in high demand, contributing to the growth of the non-invasive neuromodulation devices market.

Non-invasive treatments offer advantages over other techniques

Typically, conditions such as chronic pain are treated using a combination of prescription medicines. However, these medications, including NSAIDs, opioids, etc., come with a variety of side effects, such as digestive issues, ulcers, drowsiness, etc. Long-term use of opioids can lead to a range of negative consequences, including the development of tolerance, physical dependence, and opioid use disorder, increasing the risk of overdose and death. Conventional treatment methods also need frequent hospital visits.

Invasive neuromodulation is an effective treatment option for various neurological conditions. However, it also carries significant risks, such as site infections, perioperative and postoperative complications, blood clots, and device malfunctions. Additionally, these techniques often require multiple hospital visits.

In contrast, non-invasive neuromodulation offers several advantages over invasive methods. These wearable devices provide drug-free treatments that do not require surgery or complex installation. As a result, they are easy for patients and physicians to use.

A comprehensive study about the efficacy of various non-invasive devices is not yet available. However, controlled individual studies by companies and developers have shown promising efficiency in treating various diseases.

Moreover, a 2019 report published in BMJ, a peer-reviewed medical journal, indicated that non-invasive neuromodulation offers a potential solution for patients who are sensitive to traditional treatments. This includes patient groups such as pregnant women, adolescents, and those who experience poor tolerability or lack of efficacy from pharmacological treatment therapies.

The need to treat health conditions of these patient groups may drive the use of non-invasive devices to treat health conditions.

Scientific advancements help improve efficacy and expand applications

The non-invasive neuromodulation field has seen several breakthroughs in recent years, showing promise for accelerated R&D and new and improved devices potentially entering the market in the future.

One example is the proprietary magnetic peripheral nerve stimulation (mPNS), marketed as Axon Therapy, developed in 2023 by US-based Neuralace Medical for managing painful diabetic neuropathy.

Another example is vibrotactile stimulation (VTS), currently under development by an interdisciplinary research team from the University of Minnesota as a treatment for spasmodic torticollis or cervical dystonia. This is a painful neurological condition that affects the neck. Though the product is not yet marketable, the clinical trials are showing significant promise.

VTS devices are also being developed for conditions other than pain. An example is the VTS glove, a wearable device developed by researchers at Stanford University and the Georgia Institute of Technology in 2024. The device applies high-frequency vibrations to the hands and fingers to relieve uncontrollable arm and hand spasms. In clinical trials, patients who used the device experienced significant improvements in symptoms, with some even reporting a reduction in their use of oral medications. The team is now working to develop the device further and make it available to patients as a publicly available therapy.

Furthermore, a new treatment for tinnitus, known as bimodal neuromodulation, which involves stimulating two sensory pathways in the brain, has been developed. Ireland-based company Neuromod offers the Lenire device, which combines headphones and a mouthpiece to deliver auditory and tactile stimuli to alleviate symptoms. Patients wear the device for an hour daily, for at least six weeks, to stimulate the tongue with electrical impulses while listening to tones.

These new developments are likely to give momentum to the ongoing R&D in the sector.

Increased investment signals growing market potential

The sector has also seen an uptick in investments. For example, Nalu Medical, a US-based company, secured US$65 million in funding in 2024 to advance its neurostimulation technology for treating chronic pain.

Similarly, Avation Medical, a US-based company focusing on treating bladder issues, raised over US$22 million in 2024 to launch the Vivally System. This wearable device treats patients with urge urinary incontinence (UUI) and overactive bladder (OAB) syndrome.

Massachusetts–based Cognito Therapeutics, a company focused on developing a new therapy for Alzheimer’s disease, raised around US$73 million in 2023.

This increasing trend in R&D investments shows investors’ rising interest in the field of non-invasive neuromodulation, indicating promising market prospects.

Integration with AI is expected to pave the way for future developments

Non-invasive neuromodulation is seeing considerable success in developing closed-loop systems that leverage artificial intelligence (AI) and machine learning (ML) to give customized therapeutic output. This trend is likely to see more growth, especially with the rapid advancements in the field of AI.

An example is Avation Medical’s Vivally System, a wearable neuromodulation device that uses closed-loop, autonomously adjusted electrical stimulation to treat patients with UUI and OAB syndrome. The device uses a smartphone app to calibrate itself for each patient and then delivers a constant current of electrical stimulation through a wearable garment. It also uses an advanced AI-powered closed-loop algorithm and electromyography (a medical test that measures the electrical signals sent by nerves to muscles and received back from them) to enable continuous real-time monitoring and therapy adjustment, ensuring uniformity and safety.

Non-invasive neuromodulation device companies are forming partnerships with research institutes to develop safe ways to treat various disorders using generative AI neuromodulation.

One such collaboration started in June 2024 between US-Swiss generative neuromodulation firm, Dandelion Science and Geneva-based research institute Wyss Center for Bio and Neuroengineering. The goal is to develop a generative AI neuromodulation platform for treating neurodegenerative and neuropsychiatric disorders.

Similar collaborations are likely to commence in the future, as it is clear that the combination of neuromodulation and AI is set to impact various treatment fields significantly.

Expansion of insurance coverage could boost treatment accessibility

Conventionally, chronic pain treatment involves a combination of drugs and physical therapy. The US patient usually pays 20% of their Medicare-approved amount. People with severe pain spend about US$7,700 on annual healthcare expenditures, and with insurance, they have to spend around US$1,600 annually. For the management of pain conditions such as migraine, the out-of-pocket expense can increase to 30% of their Medicare-approved amount.

Non-invasive neuromodulation treatment has proved to be more cost-effective than conventional treatments. Although many non-invasive pain management devices are not covered by insurance, some are eligible for reimbursement.

For instance, Nerivio, a wearable device for treating migraine, is covered by Medicaid and Highmark Insurance. Moreover, Theranica, Nerivio’s Israel-based parent company, introduced the Nerivio Savings Program in October 2020 to help US patients access the device. It is a reimbursement plan that allows patients to receive their first device for a copay of up to US$49 (for 18 treatments), depending on their insurance coverage. The refill costs US$89 for those without insurance.

Additionally, patients may be able to use Health Savings Accounts (HSAs) or Flexible Spending Accounts (FSAs) to pay for specific approved devices. An example is Cefaly, for which, though not covered by insurance in the USA, consumers can use HSA and FSA funds or finance their purchase with Affirm (a US-based financial technology company that offers flexible payment options) for US$36 per month upon qualifying. Without insurance or other financial aid, the upfront cost varies from US$330 to US$430, and an additional US$25 for three reusable electrodes, each usable up to 20 times each.

Non-invasive neuromodulation devices’ high upfront cost remains the key barrier to broader adoption

Overall, non-invasive neuromodulation devices offer a more cost-effective option than other treatments. The most significant barrier for patients opting for non-invasive neuromodulation is the high upfront cost, especially with no insurance coverage.

For example, Israel-based Zida Therapeutics’ Zida Control Sock, a device to treat urinary incontinence, comes with an upfront cost of US$750. Without insurance, many people may find it challenging to cover this cost. This is particularly true for older adults whom conditions such as chronic pain and urinary incontinence affect the most. According to 2023 data released by the US Census Bureau, 14.1% of Americans aged 65 and older live in poverty, making these devices less accessible to them without insurance coverage.

However, this situation may improve as several companies are now in talks to receive insurance coverage for their devices. With an increase in R&D, companies can also offer robust evidence to demonstrate the effectiveness and long-term safety of the devices, prompting insurance companies to provide coverage.

With reimbursement available for companies such as Theranica and Zida, and with several other companies such as Neurovalens planning to enter discussions with insurance providers to achieve reimbursement status, the accessibility has a chance to improve in the near future. This will likely drive adoption in the coming years.

EOS Perspective

Adopting non-invasive devices will likely increase as a standalone treatment and adjunct therapy. While non-invasive treatments currently focus on conditions such as chronic pain, tinnitus, urinary incontinence, etc., experts believe that this will soon expand into other neurological conditions, including ALS, and Parkinson’s disease.

Currently, there are only seven FDA-approved drugs for ALS treatment, all of them with limited effectiveness. The significant unmet need in this field presents a compelling opportunity for non-invasive neuromodulation companies. Cognito Therapeutics and PathMaker Neurosystems are among the few companies conducting feasibility studies and developing non-invasive neuromodulation treatment options for ALS patients.

Research is also underway to develop a non-invasive treatment for Parkinson’s disease, which was previously treated using invasive techniques. Czech Republic-based STIMVIA has reported promising results from its initial pilot study of a new treatment for patients with Parkinson’s disease as an add-on therapy.

Several new non-invasive devices are also in the development pipeline, and their clinical trials are promising. An example that has shown positive results in a pivotal trial is a treatment for improving upper limb function by Netherlands-based ONWARD Medicals.

Non-invasive neuromodulation has the potential to revolutionize the treatment of chronic pain and other neurological disorders. As the field continues to evolve, with advancements in AI-powered wearables and increased investment in R&D, we can expect to see even more innovative solutions emerge in the coming years.

30/09/2024by EOS Intelligence EOS Intelligence No Comments

New Directions in Alzheimer’s Diagnostics: Will Blood Tests Replace CSF and PET?

Around three-fourths of dementia cases continue to remain undiagnosed even though the incidence of Alzheimer’s disease (AD) is rapidly growing across the globe. AD affects about 60-80% of dementia patients worldwide. Early diagnosis of AD is critical in forging beneficial medical care strategies and enhancing patient outcomes. Current AD diagnostic tests, such as cerebrospinal fluid (CSF) and PET scans, are either invasive or associated with side effects and are generally expensive. This calls for developing less invasive, safer, faster, and more accurate AD diagnostics, such as blood tests.

Blood-based tests promise accurate and non-invasive AD diagnosis

Researchers are developing less invasive and less costly blood tests that are likely to be more accurate than contemporary tests. There are currently two types of AD diagnostics blood-based tests: the phosphorylated tau217 (ptau217) test and the amyloid beta (Aβ) 42/40 plasma ratio test.

The ptau217 biomarker has the potential to differentiate AD from other neurodegenerative diseases, as ptau217 levels can be high in AD patients before the onset of clinical symptoms. Studies have proved that ptau217 tests can detect AD early on and monitor disease progression.

The Aβ 42/40 plasma ratio tests detect amyloid beta protein plaques in the brain that cause cognitive impairment. Due to the lack of a certified reference standard for measuring plasma Aβ42 and Aβ40’s absolute values, ptau217 may be better than an amyloid beta ratio test. However, both tests are accurate enough to diagnose AD.

Notably, ptau217 blood tests are believed to give up to 95% accurate results when coupled with CSF tests as against 90% accuracy of CSF when used as a standalone method. At the same time, amyloid beta (Aβ) 42/40 ratio tests are known to give around 80% accuracy in detecting amyloid positivity.

Many laboratories and diagnostic companies have designed or are designing ptau217 assays. C₂N Diagnostics, Quanterix, Quest Diagnostics, and Laboratory Corporation of America (LabCorp) offer ptau217 laboratory-developed tests (LDTs).

Low cost of blood-based AD tests can also be a growth-driving factor

A major push towards blood-based AD diagnostics comes from the tests’ lower cost in comparison to PET and CSF. The cost of blood tests typically ranges from US$200 to US$1,500, depending on the test provider.

The cost of PET ranges from US$1,200 to US$18,000, while the average price of CSF tests is around US$4,000 (in both cases, the actual cost depends on the type of facility, location, and the extent of insurance coverage).

As of 2023, Medicare and Medicaid covered PET scans for AD in the USA outside clinical trials. Therefore, AD patients need to pay around 20% of the PET cost, which translates to US$240-US$3,600, even after insurance coverage.

Considering the high share of dementia and AD cases remaining undiagnosed, there is a chance that the lower cost of blood-based tests can help contribute to higher accessibility to testing and ultimately improve the early detection rate.

Large AD diagnostic players partner with smaller ones to develop new tests

In an attempt to develop ptau217 assays, major diagnostics companies tend to recognize the development progress made by smaller players. ALZpath, a novel AD diagnostic solutions provider, is the pioneer of the ptau217 antibody, which helps in the early detection of the disease. Large players such as Roche and Beckman Coulter are enticed by the synergistic opportunities ALZpath offers.

In June 2024, Roche partnered with ALZpath, an early-stage biopharmaceutical company specializing in AD diagnostics, to launch the plasma ptau217 In-Vitro Diagnostic (IVD) test. As per the partnership, Roche will use ALZpath’s ptau217 antibody to design and commercialize an IVD test to detect AD with the help of Roche’s Elecsys platform.

In July 2024, Beckman Coulter also partnered with ALZpath to utilize ALZpath’s proprietary ptau217 antibody to detect AD on Beckman Coulter’s DxI 9000 Immunoassay Analyzer.

AD diagnostics firms receive funding from various sources, including drugmakers

Constantiam Biosciences, a bioinformatic analysis firm, received a US$485,000 Phase 1 SBIR grant (Small Business Innovation Research) from the National Institute on Aging to develop a tool for deciphering risk variants pertaining to AD and related dementias (AD/ADRD) in September 2024.

Biogen and Eli Lilly invested in the Diagnostics Accelerator, a funding initiative started in 2018, at the Alzheimer’s Drug Discovery Foundation (ADDF) in 2020. The Diagnostics Accelerator has invested over US$60 million across 58 projects, most of which are blood tests. In its Q4 2023 earnings call, Biogen emphasized its support for developing tau biomarker diagnostics and pathways. Its partner, Eisai, has invested around US$15 million in C₂N Diagnostics and collaborated with IVD companies such as Sysmex, among others. In September 2024, ADDF invested US$7 million in C₂N Diagnostics to further develop blood-based AD detection tests.

Other investors have also identified the opportunities AD diagnostic offers. A 2024 market research report by Market Research Future estimated that the AD diagnostic industry would nearly double, from US$4.5 billion in 2023 to US$8.8 billion in 2032.

FDA stands as an accelerating force for blood-based tests via breakthrough device designation

For a while now, the FDA has been granting breakthrough device designation (BDD) to devices that could address life-threatening diseases with unmet medical needs. BDD facilitates the expedited development, review, and assessment of medical devices, ensuring quicker access for patients and medical professionals. It would not be too ambitious to conclude that strong positive evidence from several uses and studies of ptau217 tests is likely to compel the FDA to approve them for use in the near future. The first sign of this is that the FDA is granting BDD status to multiple ptau217 blood tests.

In March 2024, the FDA granted BDD to Simoa ptau217 by Quanterix. This blood test can detect AD in patients with cognitive ailments even before signs and symptoms start to appear.

In April 2024, the FDA gave BDD to Roche’s Elecsys ptau217 plasma biomarker test to augment early diagnosis of AD. Roche partnered with Eli Lilly to develop this blood test that will widen and accelerate AD patients’ access to diagnosis and suitable medical attention and care.

In early 2019, the FDA gave BDD to C₂N Diagnostics’ blood test to detect AD. The BDD status of AD blood tests will likely accelerate the development, review, and assessment processes of these tests, improving patient outcomes.

Some FDA-approved AD drugs have used blood tests in clinical trials. Eli Lilly’s Kisunla and Esai/Biogen’s Leqembi have successfully utilized C₂N Diagnostics’ Precivity-ptau217 blood biomarker in their clinical trials. The FDA approved both drugs to manage AD. This improves the chances of this blood test getting approved by the FDA.

Lumipulse G β-Amyloid 1-42 Plasma Ratio test by Fujirebio Diagnostics received BDD from the FDA in 2019. The company submitted an FDA filing for the Lumipulse G ptau217/β-Amyloid 1-42 Plasma Ratio IVD test in September 2024. If approved, this test will become the first commercially available blood-based IVD test in the USA to detect AD.

EOS Perspective

There has been considerable progress in developing blood-based assays for AD diagnosis by pharma and diagnostics companies. However, a good portion of the liability for their products not reaching market readiness faster lies (and will probably remain to lie) on the approving authorities that are unable to accelerate the administrative steps.

Some blood tests, such as PrecivityAD, are approved for safe use in the EU but are still not in the USA. While such approval is typically a time-consuming process and requires a thorough investigation, the blood tests will enter the market at a larger scale across several geographies only if the authorities fast-track their approvals. This is particularly applicable to blood tests previously successfully used in clinical trials for approved AD drugs and for tests that have already attained BDD status from the FDA.

As an example, PrecivityAD by C₂N Diagnostics received BDD status in 2019 from the FDA. However, the FDA has still not approved the blood test for safe use in the USA. This is still despite the fact that PrecivityAD and other C₂N Diagnostics’ assays have been utilized in over 150 AD and other research studies across the USA and abroad. FDA’s time-consuming and lengthy review procedures and bureaucratic reasons are some of the factors responsible for the delay in approval. In addition to this, C₂N Diagnostics needs to submit some more evidential data pertaining to the accuracy of PrecivityAD, which is likely to take time to produce.

These procedural and administrative impediments, along with the time taken by the device makers to present the data to the FDA, will likely continue to put a brake on the blood-based tests becoming available to patients in the near future.

The situation will remain so, given the FDA’s recent decision to regulate new LDTs involving diagnostic tests that use body fluids such as blood, saliva, CSF, or tissue on similar lines as medical devices (meaning LDTs must comply with the same standards as medical devices). As per this regulation, LDTs need to prove the accuracy of their tests. This decision will have both winners and losers in the AD stakeholder ecosystem.

Researchers and physicians are looking at this regulation with a positive stride as this step will reduce the number of tests with unconfirmed accuracy from the market in the USA. This is undoubtedly a positive change for patients’ safety, reducing the number of misdiagnoses and accelerating correct diagnoses.

On the other hand, smaller start-ups and diagnostic companies are not likely to benefit from this decision as it will restrict the development of new innovative tests vis-à-vis large diagnostic companies. Overall, the decision will likely decelerate the approval of blood-based AD tests or at least will require much more paperwork and proof of accuracy from the device makers. This decision will take effect in multiple phases over four years, starting from July 2024.

On the research and development side of the Alzheimer’s disease diagnostics space, a certain level of symbiosis between drug producers and diagnostic solution providers will continue to impact the market positively. Drugmakers are partnering with or investing in diagnostic companies to leverage the latter’s innovative blood-based biomarkers (BBBM) technologies in the clinical trials of their own drug candidates. This trend is likely to continue.

Not only drugmakers but also more prominent healthcare diagnostics companies, such as Roche and Beckman Coulter, are partnering with early-stage biopharmaceutical companies, such as ALZpath, to develop and commercialize AD ptau217 tests. Collaborations such as these are a testimony to the fact that it is mutually beneficial for AD industry stakeholders to work in tandem to advance AD diagnostics research, a significant growth-driving factor for the market.

26/09/2024by EOS Intelligence EOS Intelligence No Comments

Phase 3 Drug Candidates – A Ray of Hope in Alzheimer’s Disease Bleak Treatment Landscape?

Many biopharmaceutical companies, such as AriBio, Annovis Bio, Athira Pharma, Cassava Sciences, and Alzheon, specializing in treating neurodegenerative diseases, are developing drugs for Alzheimer’s disease (AD) that are currently in phase 3 of clinical trials. If approved, these drugs can ameliorate the AD treatment approaches to a considerable extent. A major prerequisite to this is for concerned authorities to take concrete steps to fast-track clinical trials and increase AD research investment.

With only a 1% success rate of clinical trials in drug development until 2019, the AD treatment gap is alarming. A 99% failure rate means there is a very limited influx of new, more effective, and more advanced AD drugs into the market, and the gap between available treatment options and the rising number of AD cases is increasing.

The disease burden of Alzheimer’s will rise from US$1.3 trillion in 2020 to US$2.8 trillion by 2030 globally. With the rise in the aging population across the globe, the estimated number of AD patients will increase from 55 million in 2020 to 78 million in 2030.

However, recent drug approvals, such as Elli Lilly’s Kisunla (Donanemab) in July 2024 and Biogen/Eisai’s Leqembi (Lecanemab) in January 2023, bring a ray of hope for a new approach to AD treatment.

Initial hopes for new drugs can be premature

New drugs do enter the market from time to time. However, their impact on AD treatment in the long term is not always significant. An example of this is Biogen’s Aduhelm. Based on its ability to reduce amyloid protein in the brain, the FDA approved Aduhelm (Aducanumab) in 2021 in an accelerated approval route for AD treatment.

However, in 2024, Biogen discontinued the drug in the alleged desire to reprioritize its resources in AD treatment. Experts cite weak clinical evidence for efficacy, serious side effect risks, a high price point, and poor sales among the many reasons for Aduhelm’s withdrawal from the market.

AD drug candidates succumb to clinical failures

Eisai and Biogen have been working together since 2014 to develop and commercialize AD drugs. However, they have faced clinical drug failures, similarly to many other pharmaceutical companies during that time. For instance, they had to terminate Elenbecestat, one of their AD drugs, in phase 2 clinical trial in 2019 following an unfavorable risk-benefit ratio finding by the Data Safety Monitoring Board (DSMB).

Eisai launched its first AD drug, Aricept, an acetylcholinesterase inhibitor, in the USA in 1997 in collaboration with Pfizer. The annual peak sales of Aricept were US$2.74 billion before its patent expiry in 2010. However, Pfizer exited neuroscience drug research and development in 2018 after the failure of its AD drug candidates, such as Dimebon and Bapineuzumab.

Clinical challenges in Alzheimer’s research and reallocation of resources were among the other reasons for Pfizer’s exit from neuroscience R&D and drug development. Nevertheless, Pfizer did not desert the neuroscience space completely, rather forged a spin-off company called Cerevel Therapeutics in partnership with Bain Capital.

Phase 3 Drug Candidates – A Ray of Hope in Alzheimer’s Disease Bleak Treatment Landscape by EOS Intelligence

Recent drug launches focus on amyloid beta targeting mechanism

In January 2023, the FDA approved Leqembi (Lecanemab), a drug by Biogen and Eisai, for AD treatment. It is a monoclonal antibody that clears away the amyloid beta plaques known to cause cognitive impairment in AD patients. With MHRA’s (Medicines and Healthcare Products Regulatory Agency) approval of Leqembi, Great Britain becomes the first European country to authorize the drug for the treatment of early-stage AD as of August 2024.

In July 2024, the FDA approved Kisunla (Donanemab) by Eli Lilly to treat early-stage AD. The drug’s mechanism of action is the same principle as that of Leqembi, an amyloid beta protein plaque targeting mechanism. Kisunla becomes the third anti-amyloid drug approved for AD treatment, following Aduhelm (now discontinued) and Leqembi. Both Kisunla and Leqembi drugs carry the risks of the formation of temporary lumps in the brain that can be fatal. Therefore, physicians advise regular brain MRIs to alleviate this risk. Neurologists and researchers are in disagreement over whether the benefits offered by these drugs are clinically meaningful.

Researchers are still studying the side effects of these two drugs. Prescribing them requires confirmation of the presence of amyloid protein in the brain. Therefore, PET scans and CSF tests are required before such a prescription.

The FDA has approved both drugs in the USA for intravenous infusions (IV) in the early stages of AD. Kisunla is administered every four weeks instead of every two for Leqembi. Therefore, Kisunla offers greater convenience compared to Leqembi.

Experts from Bloomberg Intelligence suggest that Eli Lilly will likely surpass Biogen and Eisai’s reign at the top of the AD drug market by capturing around 50% of the US$13 billion market globally by 2030. This is partly because of Kisunla’s convenient dosing and the fact that AD patients can stop taking the drug after the amyloid levels touch the clearance threshold.

Newer therapeutic approach-based drugs are in phase 3 clinical trials

Apart from the amyloid beta therapeutic approach, AD researchers are exploring the role of other mechanisms in AD treatment, such as anti-tau antibodies, neurotransmitter receptors, and synaptic plasticity or neuroprotection. Drugs based on these mechanisms are currently in phase 3 of clinical trials.

The Washington University School of Medicine’s DIAN-TU (Dominantly Inherited Alzheimer Network Trials Unit) trial is testing Lecanemab plus Eisai’s investigational anti-tau antibody E2814 in patients with early-onset AD caused by a genetic mutation. E2814 prevents the spreading of tau seeds in the brains of AD patients. This drug is in phase 3 clinical trial. The clinical study commenced in June 2024 and will complete by November 2029.

ACP-204 by Acadia Pharmaceuticals is also in phase 3 clinical trial for AD. The agent acts as an inverse agonist at the 5-HT2A serotonin receptor. FDA has approved Acadia’s previous 5-HT2A inverse agonist, Nuplazid, for Parkinson’s disease psychosis. ACP-204 will be the first drug for AD treatment in Acadia’s product portfolio if approved.

Another drug in phase 3 trial is AriBio’s AR1001, a phosphodiesterase-5 (PDE5) inhibitor. Apart from AR1001, two more AD drugs are in AriBio’s pipeline, AR1002 and AR1003 that are currently under the investigational new drug-enabling stage of clinical trials.

For better patient outcomes, researchers are attempting to develop AD drugs with non-invasive modes of administration that are likely to be less expensive and equally effective compared to AD drugs administered intravenously.

The safety and effectiveness of oral therapy candidate Buntanetap, developed by Annovis Bio, are comparable in people with early onset AD regardless of whether they do or do not carry a genetic risk factor APOE4. That is according to new data from a phase 2/3 clinical trial that tested three doses of Buntanetap against a placebo in more than 300 patients with the neurodegenerative disease. Buntanetap modulates protein production to reduce clumping. The competitive advantage of Annovis Bio over its peers is the fact that Buntanetap targets multiple proteins in the brain, such as amyloid beta, tau, alpha-synuclein, and TDP43, making it more effective than AD drugs that target a single protein.

Apart from Buntanetap, Annovis Bio has another oral drug to treat advanced AD and dementia in its pipeline, ANVS301, which is in phase 1 of clinical trial. In July 2024, Annovis Bio received FDA approval to transition to a new solid form of Buntanetap in future clinical trials allowing the company to refine its drug formulation, potentially improving its efficacy and safety profiles.

Another promising AD drug candidate, Fosgonimeton by Athira Pharma, is a small-molecule positive modulator of the hepatocyte growth factor (HGF) system, previously showing neuroprotective, neurotrophic, and anti-inflammatory effects in preclinical models of dementia. This drug is in phase 3 clinical trial. Athira Pharma ended 2023 with a strong balance sheet, signaling its better financial position to augment its ongoing pipeline development.

Eli Lilly’s new drug Remternetug works as pyroglutamyl (3)-amyloid beta-protein (3-42) inhibitors, positioning it as a promising AD drug. Remternetug will join Eli Lilly’s portfolio as a second AD drug if approved.

Simufilam by Cassava Sciences is a proprietary, small-molecule oral drug that restores the normal shape and function of altered filamin A (FLNA), a scaffolding protein, in the brain. It is now in phase 3 clinical study to test this new and promising scientific approach to treating and diagnosing AD. The mechanism of action of this drug involves stabilizing a critical protein in the brain instead of removing it. This novel approach distinguishes Cassava Sciences’ drug from other treatments that predominantly focus on amyloid-beta or tau proteins. In May 2024, Cassava Sciences raised US$125 million by selling its stock to shareholders. The funds will be utilized for the continued development of Simufilam.

Valiltramiprosate by Alzheon is potentially the first oral disease-modifying treatment for AD. Valiltramiprosate is well differentiated from plaque-clearing antibodies in development for AD due to its novel mechanism of action, oral mode of administration, and potential efficacy in a genetically targeted population. In October 2017, Valiltramiprosate/ALZ-801 received FDA Fast Track designation for AD investigation. Due to Alzheon’s significant progress in AD drug development, the company has attracted a lot of investors since 2022. Alzheon received US$100 million in June 2024 in Series E venture capital funding which will be utilized to further develop and commercialize Valiltramiprosate. This is in addition to US$50 million received in series D round of funding in 2022.

Big names dominate the competition, with clinical trials in progress by smaller biopharma players

On the competitive landscape front, the AD drug market is highly competitive, with many pharmaceutical companies financing R&D to engineer new drugs that could potentially delay the progression of AD and/or restore neuronal health. The global AD therapeutics market size was US$4.8 billion in 2023 and will surpass US$7.5 billion by 2031, as per Towards Healthcare, a healthcare consulting firm.

A couple of large players still dominate the global AD therapeutics market. Interestingly, they are not the only ones active in the AD treatment development, as several smaller biopharmaceutical companies that specialize in neurodegenerative disease treatment are working on AD drugs (many currently in phase 3 of clinical trials).

High R&D costs are a considerable factor in slowing the progress down

Between 1995 and 2021, the cumulative private spend (total R&D expenditure by pharmaceutical companies, does not include federal funding) on clinical stage R&D for AD was US$42.5 billion, with the largest share of 57% (US$24.1 billion) incurred during phase 3. During the same period, the FDA approved 878 drugs across all therapeutic areas; only six of these drugs were for AD treatment (four cholinesterase inhibitors [ChEIs], memantine, and aducanumab). These statistics speak volumes of the complex, expensive, time-consuming, and predominantly unsuccessful nature of AD clinical trials. This ultimately leads to exorbitant prices of AD drugs.

A range of factors drive the R&D costs and, in turn, the price of AD drugs. A significant component here is patient screening, which contributes to 50-70% of the cost. Patient recruitment and retention are also challenging, given the considerable length of such trials.

Moreover, patient recruitment challenges stunt the progress of AD clinical trials. The recruitment rate for AD clinical trials is as low as one patient per site per month. In terms of eligibility, 99% of AD patients who are eligible for participation in a clinical trial never consider taking part. This further increases the time taken to conduct AD clinical trials.

EOS Perspective

After decades of failure in clinical trials, two anti-amyloid AD drugs, Kisunla and Leqembi, are available in the market, forming a duopoly in the USA. There are several promising drugs in phase 3 clinical trials with a new mechanism of action apart from amyloid beta protein inhibitors. However, the disease management landscape is prone to unforeseen changes, such as the withdrawal of drugs owing to safety, efficacy, and pricing issues.

The AD treatment landscape faces challenges such as drug inefficacy, complex pathophysiology of AD, expensive and time-consuming clinical trials, delays in diagnosis by physicians, behavioral changes and deteriorating mental health of AD patients, and severe side effects of medications. These challenges will continue to impede the development of new disease management approaches.

An issue that is very likely to continue to challenge progress in developing better treatment options for AD is the severe lack of funding. Dementia research is extremely underfunded compared to HIV/AIDS, cancer, and COVID-19 in the USA. Irrespective of the fact that the deaths attributed to AD are on par with cancer, the difference between the annual US federal government funding for AD vis-à-vis cancer is strikingly huge.

AD drug development is a tough market to operate in. The ongoing issue with AD research funding persists, and there do not seem to be changes in federal funding soon. On top of that, the slow progress in successful R&D and many failed clinical research trials will likely make private-sector investors hesitate or withdraw.

In addition to this, AD drug manufacturers will also continue to face the challenge of low to modest drug sales due to poor adoption rates stemming from issues like restricted coverage.

As of June 2023, Medicare was covering AD drugs that slow down the progress of the disease provided a physician agrees to the collection of real-world evidence of these AD drugs, as per the Centers for Medicare & Medicaid Services (CMS). However, there is a significant underlying problem with drugs for AD treatment. When the drug finally enters the market, patients cannot afford the treatment, and the coverage is restricted and sometimes withdrawn. There is no foreseeable change to this impasse, and hence, the AD treatment development is likely to be slow.

If reimbursement of AD drugs is removed, patients are likely to stop administering AD drugs altogether and adopt alternative healthcare resources such as antidepressants, as found in a 2021 study by researchers from Paris-Saclay University and Memory Center of Sainte Périne Hospital in France.

The reluctance of payers to cover the treatment cost for AD is influenced by several factors beyond just the high cost of the drug. Factors include cost-effectiveness of treatments, uncertain long-term safety and efficacy benefits of treatments, clinical guidelines and recommendations, availability of alternative treatments including generics (from drug makers such as Cadila, Cipla, Dr. Reddy’s, among others), and regulatory and reimbursement policies.

The future of AD treatment approaches will continue to remain bleak, and patients will be left with only a few available drug options unless the right authorities set out a plan for fast-track clinical trial processes, increase AD research investment, and support broader insurance coverage.

19/09/2024by EOS Intelligence EOS Intelligence No Comments

Pharma Companies Navigate Their Way through Ac-225 amidst Supply Constraints

Pharma companies have been increasingly investing in developing targeted alpha therapies for cancer treatment, using alpha-emitting isotopes such as Ac-225. However, the current supply for Ac-225 is limited, and thus, companies are working towards securing their supply chain. The recent investment by Eli Lilly in isotope manufacturer Ionetix brings to light the increasing interest of large pharmaceutical companies in Ac-225 and its uninterrupted supply for their pipelines. Similar to Eli Lilly, several other companies have strategically invested in or partnered with manufacturers to ensure a guaranteed supply.

Ac-225 is pegged as a promising isotope for next-generation cancer treatment

Among the recent advances in cancer therapies, only a few have shown as much promise as targeted alpha therapies have. Targeted alpha therapies (TAT) involve using alpha-emitting isotopes to selectively target and destroy cancerous tissue without causing significant damage to surrounding healthy tissue. This is facilitated by the short range of alpha radiation in human tissue (less than 0.1 mm), which corresponds to less than 10 cell diameters. Moreover, they are characterized by high energy levels (5-9 MeV), which results in the selective destruction of malignant cells.

Several alpha-emitting isotopes are currently being explored for TAT, the most common among them being Ac-225, At-211, Pb-212, and Bi-213. Of these, Ac-225 (actinium-225) is considered the most potent medical-grade radioisotope as it has a high decay energy of 5.9 MeV and a half-life of 10 days. It is the isotope of choice in several clinical trials, with about 15 Ac-225-based ongoing clinical trials currently in the USA. However, despite having substantial potential for developing next-generation treatments in the cancer space, their adoption has been slow, given the short supply of the isotope.

Ac-225 is not naturally available and is derived from Th-229 (thorium-229), a byproduct of uranium-233 (U-233), which is a leftover from the production of atomic weapons in the 1950s and 1960s. The initial batch of Ac-225 has been supplied by the US Department of Energy (DOE). However, the supply cannot keep up with the growing demand for trials.

Isotope producers invest to accelerate Ac-225 supply in the future

Currently, there are two commercialized routes to produce Ac-225. As mentioned above, the first and traditional route involves separating Ac-225 from Th-229, derived from the US government’s legacy reserves of U-233. The US government holds about 453kg of U-233, of which only about 256kg is of high quality and will produce about 24g of medical-grade thorium.

The government had previously started a program that extracted a small amount (150mCi) of Th-229, which produced about 1.2 Ci of Ac-225 per annum, enough to treat 1,200 patients. However, in 2019, the US DOE entered into a public-private partnership with Terra Power and Isotek to downblend its stock of U-233 to extract Th-229, which can further be used to develop Ac-225. In 2021, TerraPower entered into an agreement with Cardinal Health, a US-based commercial alpha contract manufacturing organization (CMO), to develop and produce Ac-225 for drug development commercial sales. This will likely significantly improve the supply of Ac-225 in the long run.

The other route to produce Ac-225 is through cyclotron production, which involves irradiating a Ra-226 (Radium-226) target with a proton and knocking off two neutrons. Several isotope manufacturers are adopting this technology and are working on increasing their manufacturing capacity.

Niowave, a US-based supplier of medical and industrial radioisotopes, uses a closed-loop cycle to produce high-purity Ac-225 and other alpha emitters from Ra-226 using a superconducting electron linear accelerator. Similarly, Ionetix, a leading cyclotron technology innovator and isotope manufacturer, uses the same technology to produce Ac-225 and managed to produce its first batch of Ac-225 in June 2024. The company commissioned its first cyclotron at its current facility in 2023, while it aims to install and commission a second cyclotron there in early 2025. By 2025, it is expected that the company will be able to produce about 1Ci per week. The company also aims to establish another site in the USA for Ac-225 production in 2026.

While isotope manufacturers are strategically working to enhance the production of Ac-225 in the long run, the current supply, which is required to fuel the ongoing clinical trials using Ac-225, is quite limited. In 2024, the worldwide supply of Ac-225 is estimated to be about 2Ci per annum, which is merely enough to treat 2,000 patients.

Pharma companies invest in securing their Ac-225 supply chain

Given its currently limited availability and immense potential, leading pharmaceutical players are adopting various strategies to secure their Ac-225 supply to support their targeted alpha therapies drug pipelines. Several leading players, such as Fusion Pharmaceuticals, Telix Pharmaceuticals, and Bayer, are actively working on partnering with companies producing Ac-225 to overcome supply-related challenges for their trials. Recently, a leading pharmaceutical company, Eli Lilly, also joined the bandwagon and secured its supply of the actinium isotope.

Fusion, which has three Ac-225-based drugs currently under trial, was one of the first movers in this regard and has inked several partner agreements to ensure a smooth supply.

In December 2020, Fusion entered into a partnership with TRIUMF, Canada’s national particle accelerator center. In this partnership, Fusion would provide the latter with up to US$18.5 million (CA$25 million) to upgrade its production facilities and scale up production of Ac-225. In return, Fusion would receive preferred access and pricing to the resulting isotope.

In June 2022, Fusion collaborated with Niowave, a US radioisotope manufacturer. Under the agreement, Fusion would invest up to US$5 million in Niowave to further develop their technology to increase their production capacity of Ac-225. In return, Fusion will be guaranteed access to a pre-determined percentage of Niowave’s capacity of the resulting Ac-225, as well as preferred access to any excess stock produced.

In November 2023, Fusion entered into an agreement with BWXT Medical, a US-based supplier of nuclear components and a subsidiary of BWX Technologies. Under the agreement, the latter agreed to provide Fusion with a preferential supply of Ra-225 (parent isotope of Ac-225) and access to high-specific activity generator technology. This would enable Fusion to produce Ac-225 at its own manufacturing facility for use in clinical trials. In addition, BMXT Medical provides Fusion with predetermined amounts of its actinium supply needs under a preferred partner agreement.

Another leading radiopharmaceutical player, Telix Pharmaceuticals, entered into an agreement with Cardinal Health in May 2024 to supply Ac-225 globally.

Similarly, in February 2024, Bayer signed an agreement with PanTera (a Belgian radioisotope production JV created by Ion Beam Applications and SCK CEN) to secure large-scale production of Ac-225. PanTera uses both the Ra-226 and Th-229 production mechanisms to produce Ac-225. It is collaborating with TerraPower to supply Th-229.

Eli Lilly, the largest pharmaceutical company globally, has also recently invested in a nuclear isotope manufacturing company, Ionetix, in August 2024. Eli Lilly has made a US$10 million convertible loan investment in the company to secure its supply of Ac-225. Moreover, PointBiopharma, which was acquired by Eli Lilly in 2023, also had a previous US$10 million investment in Ionetix, resulting in Eli Lilly holding a total of US$20 million debt facility with Ionetix. The pharma giant has the option to convert this debt into equity when Ionetix’s valuation exceeds US$300 million.

These investments by Eli Lilly and Fusion Pharmaceuticals are rare cases where major pharmaceutical companies are investing up the supply chain to secure actinium availability for their cutting-edge drug pipelines.

EOS Perspective

While targeted alpha therapies are emerging as high-potential next-generation cancer drugs, they are plagued by supply constraints of alpha-emitting isotopes, especially Ac-225. Thus, companies seeing great promise in these therapies must work towards securing their supply of these isotopes to ensure the smooth running of their clinical trials.

In the past, large pharmaceutical companies such as BMS have had to halt enrolment in their clinical trials due to the non-availability of Ac-225. Such interruptions not only delay the entire clinical trial but also have significant cost implications and could jeopardize its overall success.

Considering these limitations, it is imperative that pharmaceutical companies with ongoing or planned Ac-225-based trials invest in ensuring a guaranteed supply of the isotope for the entirety of their trial and future production of the drug once approved. While several companies are merely entering into supply agreements with isotope manufacturers, others are taking it one step ahead and investing in their upstream suppliers. Moreover, some companies, such as Fusion and now BMS, are advancing towards building on-site production of Ac-225.

That being said, establishing a secure supply chain of Ac-225 comes with its own set of costs and risks. Most pharmaceutical companies are undertaking significant investments (ranging between US$5-25 million) to guarantee their supply of Ac-225.

However, as a cancer therapy, TAT is in the nascent stages of development, and most trials utilizing Ac-225 are still in either phase 1 or phase 1/2, far from FDA approval. Moreover, the only Ac-225-based trial in phase 3 is being conducted by BMS for neuroendocrine cancer and is currently halted due to supply issues. Given the nascency and early stages of development of this treatment, it is too soon to predict if these heavy investments into Ac-225 would result in the development of FDA-approved drugs and bring sufficient returns. This risk can have particularly dire consequences for small players.

Thus, while companies looking to develop targeted alpha therapies using Ac-225 must work to secure their supply, their level of investment must remain in sober relation to their size, pipeline, and financial position.

14/08/2024by EOS Intelligence EOS Intelligence No Comments

Prescribing Security: Diagnosing and Treating the IoT Universe in Healthcare

The integration of the Internet of Things (IoT) into the healthcare industry has significantly transformed the delivery of medical services, enhanced patient experiences, and revolutionized medical practices. While the benefits of IoT are undeniable, there are challenges that come with its adoption. Issues such as device hacking and data breaches pose significant obstacles that must be addressed. Therefore, it is essential for device manufacturers to design medical devices with caution. By taking a proactive approach and investing in robust cybersecurity measures during the design and development phases, manufacturers can create devices that are more secure and less vulnerable to hacking.

IoT has revolutionized the healthcare industry by enabling medical devices to connect and communicate with each other, as well as with healthcare providers and patients. These devices utilize cloud computing and collect valuable data in real time, allowing for remote monitoring, timely interventions, and personalized care.

The average hospital room worldwide has an estimated 15 to 20 interconnected medical devices. This number is steadily increasing due to the rising adoption of internet-connected devices. The market for IoT medical devices is close to US$40 billion as of 2023. With exponential growth, it is likely to cross US$150 billion over the next five years. This upward trajectory is geared towards reducing healthcare systems’ costs, enhancing patient care, and streamlining clinician workflows.

Healthcare organizations are not immune to cybersecurity breaches

Amid this inevitable growth in adoption, it is crucial to prioritize the security of medical devices to protect patients’ lives, safety, and privacy. While these devices have the potential to streamline and improve treatment, they also pose significant risks due to their susceptibility to cyberattacks.

According to a 2019 report by Fierce Healthcare, 82% of healthcare organizations experienced cyberattacks targeting IoT devices. Moreover, about 53% of medical and IoT devices in hospitals had vulnerabilities. Cybercriminals have honed in on the healthcare industry as a prime target, capitalizing on its perceived lack of robust cybersecurity protocols.

Healthcare bleeds out money without a cybersecurity cure

According to IBM’s Cost of a Data Breach 2023 report, the average cost of a cyberattack in the healthcare industry is US$4.45 million per breach, marking a 2.3% increase from the previous year’s average cost of US$4.35 million.

This significant uptick in costs since 2020, when the average overall cost of a data breach was US$3.86 million, represents a substantial 15.3% increase over three years. This growth underscores the importance of prioritizing cybersecurity measures to protect sensitive patient data and ensure the safety and integrity of medical devices in healthcare settings.

Unaddressed IoT challenges in medical devices lead to unauthorized access

Despite the many potential benefits of IoT medical devices in healthcare, the lack of adequate security measures continues to be one of their main challenges. Many devices do not have robust encryption protocols or authentication mechanisms, making them easy targets for hackers.

These vulnerabilities could potentially be exploited to gain unauthorized access to patient information or manipulate the device to deliver harmful treatments. As these devices become more interconnected with other healthcare systems, the potential cyberattacks only increase, posing a serious threat to patient safety.

Prescribing Security Diagnosing and Treating the IoT Universe in Healthcare by EOS Intelligence

Hackers endanger patients’ health and lives

Hackers can exploit vulnerabilities in IoT medical devices to gain access to sensitive patient information, alter treatment settings, or sabotage critical systems. This poses a grave threat to patient safety and privacy, as well as the overall integrity of healthcare infrastructure. Furthermore, since IoT devices are interconnected, a breach in one device could potentially compromise the entire network, leading to widespread disruptions and chaos in healthcare delivery.

One example of such a breach occurred in 2019 at a Springhill Medical Centre in the USA involving a ransomware attack. This attack disabled patient monitors for several days, leading to a substantial impact on patient care. A lawsuit has been filed, alleging that the disabled monitoring devices led to infant death during delivery at the center.

IoT medical devices need improved security to match technological advancements

The rapid pace of technological advancements in IoT medical devices often outpaces the development of security protocols. New features and functionalities are constantly added to these devices to improve patient care.

However, these updates may also introduce additional security vulnerabilities that cybercriminals can exploit. Many healthcare providers struggle to keep up with these evolving threats and may not have the resources or expertise to effectively secure their IoT devices on an ongoing basis.

Diversity of IoT devices complicates securing healthcare environments

The healthcare environment is characterized by a diverse range of interconnected devices, often developed by various manufacturers with varying security protocols, making it difficult to implement a cohesive security strategy across all devices. This diversity complicates efforts to achieve comprehensive visibility and security, as each device may require distinct monitoring and protection strategies.

Additionally, the sheer number of devices in use within a healthcare facility can overwhelm IT teams responsible for monitoring and securing them, increasing the likelihood of overlooking potential security risks.

Limited downtime poses cybersecurity challenges

IoT medical devices are used continuously in real time, leaving little room for downtime. This lack of downtime poses a challenge for security teams, as they have limited time to analyze the devices and implement necessary patches to ensure their security.

The constant use of these devices in healthcare settings highlights the importance of finding a balance between security and functionality in order to safeguard sensitive patient data and uphold the integrity of the healthcare system.

Devices’ size and continuous connection result in insufficient battery support

Another challenge in the realm of IoT devices is related to their powering. Many of these devices use batteries and their compact size restricts the capacity for large, durable batteries. They need to be constantly connected to transmit data, which continually drains power.

These devices’ limited power and memory make it difficult to incorporate encryption, continuous software updates, and authentication protocols that can protect sensitive patient information from hackers.

Durability of IoT medical devices poses a security risk

Additionally, IoT medical devices are engineered to have a long lifespan. Their durability can pose a security risk. Once a vendor ceases production or stops releasing updates for these devices, hospitals may continue to rely on outdated technology, making them vulnerable to cyberattacks.

Hospitals must play a role in safeguarding their IoT device systems

Securing healthcare IoT devices can be a complex task, but it is essential to implement a variety of solutions to guarantee their security.

Part of this responsibility lies on the healthcare institutions themselves. Hospitals must ensure regular software updates, avoid default settings, and provide comprehensive training to staff members. Healthcare providers must implement unique and multilayered login structures for every device, such as two-step logins, hard-coded passwords, firewalls, and fingerprint checks to ensure that patient information is securely stored.

Leading players’ solutions increase devices’ resilience to breaches

Advanced and complex security solutions

Prominent vendors, such as Medigate, Medcrypt, and Cynerio, provide advanced platforms designed to assist healthcare organizations in safeguarding their networks and connected medical devices.

These security vendors offer complex security solutions, including real-time threat detection, device monitoring, network activity visibility to medical device manufacturers, and vulnerability management solutions to enable healthcare providers to effectively identify and mitigate potential risks associated with their connected medical devices.

Detection and recovery plan

Cybersecurity providers are generally vigilant in offering detection and recovery services to safeguard medical assets and systems around the clock. In the event of a security breach, they must be able to swiftly implement response and recovery plans to mitigate the impact. With a focus on healthcare, they must be able to identify issues efficiently without overwhelming users with excessive information. They need to aim at taking instant action to restore normalcy as quickly as possible.

Network segmentation

Another important solution players should provide is network segmentation, which involves dividing devices into separate, private wireless networks to protect data in the event of a cyberattack. Firewalls and multi-factor authentication can achieve this. By segmenting the network into distinct zones, healthcare providers can isolate medical devices from other parts of the network, reducing the risk of a cyberattack spreading across the entire network. This segmentation also allows for more granular control over medical devices, limiting the potential for unauthorized access or tampering.

Modern network segmentation for medical devices now relies on technologies such as virtual LANs and subnets to keep up with advanced cyber threats. For instance, Cisco Systems, a multinational technology conglomerate, offers medical device security solutions whose key aspect is network segmentation. Cisco also provides specialized monitoring and analytics tools to assist healthcare organizations in detecting and responding to security incidents in real time. These tools can identify abnormal behavior on the network, alerting security teams to potential threats before they can cause harm.

AI technology and machine learning

IoT device security providers, such as IBM Corporation, Cylera, CyberMDX, Sternum, ClearDATA, and Palo Alto Networks, place emphasis on conducting comprehensive risk assessments during software validation to guarantee devices’ security. In the event of new cyberattacks, these providers inform stakeholders and offer solutions, such as security updates. They have integrated programs that utilize AI technology and machine learning to proactively manage risks and stay ahead of cybersecurity threats.

Security vendors contribute to IoT device safety protocols transformation

The cybersecurity industry is currently experiencing a surge of new companies that are transforming security protocols. Armis, a leading US-based asset intelligence cybersecurity company and provider of agentless device security solutions, is spearheading this movement.

Notably, Medtronic and Zimmer Biomet have incorporated Armis’ security platform into their products, such as insulin pumps and orthopedic devices. Armis offers the Armis Centrix platform, powered by the Armis AI-driven Asset Intelligence Engine. The platform has the capability to detect breaches, run routine security scans or updates, maintain asset visibility, identify blind spots, optimize resource allocation, and perform essential maintenance. Armis’ solutions encompass advanced threat intelligence and machine learning features, enabling the system to adapt to new and emerging threats. This proactive cybersecurity approach is essential in the healthcare sector, where any disruption or compromising of medical devices could have severe repercussions.

Collaboration is key to effectively managing cyberattacks

Collaborations between medical device manufacturers and cybersecurity vendors to combat IoT medical device hacking have great potential. It also facilitates the sharing of threat intelligence and best practices, enabling vendors and manufacturers to proactively address emerging threats and vulnerabilities. Their collaborative efforts center on safeguarding critical devices from cyber risks by implementing protective measures for both the devices and the data they collect.

Philips partnered with CyberMDX to create a vendor-neutral cybersecurity service

In November 2020, Philips, a prominent player in healthcare technology, partnered with CyberMDX, a cybersecurity expert specializing in medical devices. This partnership focused on enhancing the security of connected medical devices and systems, essential for protecting patient data and for the smooth operation of healthcare facilities.

Drawing from Philips’ industry expertise and CyberMDX’s cybersecurity solutions, together they provide vendor-neutral options to protect IoT medical devices. They focus on managing connected devices in hospital settings, whether they are managed or unmanaged, by utilizing a combination of risk assessment, detection, threat intelligence, and prevention capabilities in the constantly evolving healthcare technology landscape.

Medcrypt collaborated with NetRise to address cybersecurity issues

In August 2023, Medcrypt, a US-based proactive cybersecurity provider, partnered with NetRise, another US-based cybersecurity company. By combining Medcrypt’s experience in identifying and managing vulnerabilities with NetRise’s ability to develop Mobile Device Management software featuring a Software Bill of Materials (SBOM) for embedded devices and firmware, medical device manufacturers now have access to a comprehensive solution to protect their devices from potential cyber threats throughout their lifecycle.

Medcrypt integrated NetRise’s SBOM generation capabilities into the Helm tool, enabling continuous integration, analysis, and transparency of the ever-changing state of medical device software. This integration facilitates the proactive identification and mitigation of the most exploitable vulnerabilities, extending support for SBOMs across the entire lifecycle of medical devices. The resulting solution empowers medical device manufacturers to create, ingest, enhance, manage, and monitor SBOMs, providing invaluable insights into the vulnerabilities present in their embedded devices and firmware. This collaboration represents a significant advancement in bolstering cybersecurity measures within the healthcare industry.

The industry is moving towards Trojan-free devices to safeguard against cyberattacks

Among the various cybersecurity threats faced by IoT medical devices, hardware Trojans are emerging as a grave concern. Hardware Trojans involve the deliberate manipulation of an integrated circuit or electronic device to compromise its security features or functionality.

Hardware Trojans are typically small in size, consist of only a few gates, and alter the device chip’s functionality. Due to their small size, hardware Trojans are challenging to detect using traditional offline methods such as side-channel analysis or digital systems testing. As a result, the healthcare industry is increasingly prioritizing the development of Trojan-free medical devices to enhance the security of IoT medical devices.

Unlike other medical devices, Trojan-free devices are highly secure and challenging to breach. Attackers would need a high level of expertise to understand the device’s design blueprint through reverse engineering and then create a manipulation that can only be triggered under specific conditions.

Moreover, the development of Trojan-free medical devices presents a unique opportunity for manufacturers to drive innovation, improve patient care, advance cybersecurity solutions, and shape regulatory standards.

One example of a Trojan-free medical device is the Philips IntelliVue patient monitor, which tracks patients’ vital signs and provide real-time data. This device works with advanced network security measures, including firewalls, encryption, and intrusion detection/prevention systems, to safeguard against unauthorized access and malware infiltration. Its cybersecurity features are specifically designed to protect against potential threats such as unauthorized access and data breaches.

Boston Scientific’s S-ICD implantable cardioverter-defibrillator is another Trojan-free medical device. It treats patients at risk of sudden cardiac arrest by delivering an electric shock to restore normal heart rhythm. This device employs encryption to secure communication between the device and the programmer and authentication protocols to ensure that only authorized healthcare professionals can access and control it.

EOS Perspective

IoT has transformed numerous industries, with healthcare being no exception. In the realm of healthcare, IoT medical devices utilized in virtual wards, such as remote monitoring devices and wearable sensors, are susceptible to cyberattacks. These attacks can result in unauthorized access, data tampering, and disruption of patient care. Detecting and responding to cyber threats targeting medical devices is crucial.

To combat these threats, security vendors employed prevention systems, anomaly detection algorithms, and advanced analytics to identify potential cyberattacks and abnormal device behavior. Implementing robust incident response plans, conducting simulated exercises, and utilizing strong device security measures is imperative to safeguard against device-level cyber risks.

The field of cybersecurity in healthcare is intricate and constantly evolving. Addressing cybersecurity risks necessitates a comprehensive approach that encompasses technology, policies, regulations, and education. Continuous collaboration, vigilance, and adaptation to emerging threats are essential to ensure the security and safety of medical devices in the future.

Moreover, healthcare facilities must prioritize the implementation of robust device security risk management practices. This involves establishing standard protocols, automating device isolation, utilizing asset intelligence to minimize security breaches, and ensuring compliance with regulatory frameworks such as HIPAA, FDA, ISO 13485, and HITRUST when acquiring and managing connected medical devices.

In addition, healthcare facilities must provide comprehensive training to professionals who work with these devices on cybersecurity best practices and identifying potential security threats.

Collaboration between healthcare providers, device manufacturers, cybersecurity experts, and regulatory bodies is essential for enhancing the security of medical IoT devices. By sharing knowledge, resources, and best practices, stakeholders can collectively address vulnerabilities and safeguard healthcare systems.

Their collaborative efforts facilitate the adoption of SBOM formats, threat modeling processes, Secure Product Development Framework, encryption technologies, AI-based anomaly detection, regulatory frameworks, and secure hardware modules. This approach ensures a more secure environment for medical IoT devices and ultimately protects patient data and healthcare systems from potential cyber threats.

Innovations such as blockchain technology, biometric authentication, predictive analytics, regular patching or updates, and Trojan-free medical devices offer promising opportunities to enhance security measures in the healthcare sector. Trojan-free medical devices, in particular, show great potential in safeguarding patient data, ensuring device integrity, and maintaining the trustworthiness of healthcare technology. This not only improves device reliability but also reduces downtime, benefiting both patients and healthcare providers. This is likely the direction the industry will take in the long run.

By prioritizing proactive cybersecurity measures and compliance with regulations, healthcare security providers can offer potential solutions to enhance the security and integrity of medical devices and the data they handle.

25/07/2024by EOS Intelligence EOS Intelligence No Comments

Lessons for Africa: To-do’s from India’s Successful Vaccine Journey

India, still a developing country, has achieved tremendous success as the world’s largest vaccine producer. This accomplishment leads to many lessons that India can offer to other low- to middle-income economies across the globe, such as Africa, looking to ramp up their vaccine industry. The African continent should capitalize on this opportunity and seek guidance from India, considering that India’s pharma and vaccine sectors are four to five decades ahead of the African continent.

How did it all begin for the Indian pharma and vaccine sectors?

The Indian pharma industry is more than a century old, with the first pharmaceutical company founded in 1901 and started operations in Calcutta. Till 1970, the Indian pharmaceutical industry comprised foreign players with very few local companies. However, driven by the purpose of the Swadeshi (meaning ‘of one’s own nation’) movement during the pre-independence era, some pharmaceutical manufacturing firms were founded in India. Established in 1935 in Bombay, Cipla was one such company, which is now a multinational pharmaceutical firm.

Apart from pharma companies, the presence of the Bombay-based Haffkine Institute (founded in 1899) and Coonoor-based Pasteur Institute of India (founded in 1907) solidified the country’s vaccine industry foundation. These institutes manufactured anti-plague, anti-rabies, smallpox, influenza, and cholera vaccines, among others. Nevertheless, the British colonial government in India withdrew the funds during World War II, which led to the subsidence of a few of these institutes.

The Indian pharma industry’s dynamics began to change, with recognition given to process patents instead of product patents. This created an opportunity for local pharma companies to reverse-engineer branded drugs’ formulations. It also allowed the creation of low-cost medicines since the producers did not have to pay royalties to original patent holders. It fueled the generics market growth in India, along with improving the capabilities of the manufacturers to produce high volume at low cost, thereby increasing the cost-effectiveness of the products. This was followed by the exit of foreign pharma players from the country with the removal of the Indian Patents and Design Act of 1911 and the implementation of the Government’s Patents Act of 1970.

This article is part of EOS' Perspectives series on vaccines landscape in Africa. 
Read our other Perspectives in the series:

Vaccines in Africa: Pursuit of Reducing Over-Dependence on Imports

Why Can India’s Vaccine Success Story Be a Sure Shot Template for Africa?

The structural change in the Indian pharma industry was evident from the drastic increase in the number of domestic companies from 2,000 in 1970 to 24,000 in 1995, leapfrogging 12-fold in a span of 25 years.

Additionally, driven by public sector investment and the central government’s prioritization of localized vaccine and drug production, India had over 19 public sector institutes and enterprises by 1971 that produced vaccines and generic drugs. These public sector institutes included Gurgaon-based Indian Drugs and Pharmaceuticals Limited and Pune-based Hindustan Antibiotics Limited.

Some pharma companies entered the export market owing to the 1991 liberalization of the Indian economy, the experience gained from producing cost-effective generic drugs, and global expansion. With this step, the Indian vaccine industry forayed into the international market between 1995 and 2005.

The reintroduction of the product patent system encouraged foreign pharma firms to return to India as the 2005 Patents (Amendment) Act prevented domestic pharma companies from reverse engineering formulations of branded medicines protected by patents to produce generic drugs.

In the pursuit of staying competitive with their foreign peers, Indian pharmaceutical companies focused on improving R&D thereby increasing investments in this space from 2005 to 2018.

What did India do right in vaccine manufacturing?

From investing in education and R&D to making necessary policy changes conducive to the growth of a sustainable and resilient vaccine sector, the Indian government has always been at the forefront of reducing overall pharmaceutical costs and nurturing the pharma industry.

Experience, expertise, and conducive policies enabled India to achieve cost-effectiveness

Indian government’s concrete action in strategy and policy-making has empowered the pharma industry to grow in a conducive environment. These conditions enabled the sector to become cost-effective by producing low-cost generic medicines and vaccines at high volumes.

This is evident from the fact that Invest India, the country’s investment promotion agency, states that producing pharmaceuticals in India is 33% cheaper than in Western markets due to labor costs being 50-55% lower. The cost of conducting clinical trials in India is also much lower, approximately 40%-80% cheaper when compared to Western markets, according to a 2010 article by the International Journal of Pharmacy and Pharmaceutical Sciences.

Indian pharma firms sometimes reverse-engineer medicines produced by companies making branded drugs and sell the formulation at a much-reduced price. The unique selling proposition of the Indian pharma industry has always been high volume coupled with low costs to make its products more affordable and accessible to patients across low- to middle-income strata of society.

Investments towards a robust scientific workforce helped reduce API import dependencies

Backed by the central government’s prioritization of domestic vaccine and drug production, some pharma companies in India started manufacturing raw materials or key starting materials to minimize the dependencies on API imports.

Other initiatives to strengthen the foothold of the Indian vaccine sector were directed towards building a solid talent pool of professionals who could develop drugs and vaccines independently rather than copy the processes from branded medicines. A result of this approach was the Lucknow-based Central Drug Research Institute (CDRI), which was founded in 1951 and continues to be one of the leading scientific institutes in India.

With the creation of the Department of Biotechnology (DBT) in 1986, India took another massive step towards progressing its pharma industry. Since then, DBT has been at the forefront of providing financial and logistical support for vaccine development and production using new and advanced technologies. The organization is also involved in creating biotech training programs for universities and institutes across India.

Lessons for Africa To-do’s from India’s Successful Vaccine Journey by EOS Intelligence

What can Africa learn from India’s experience?

It would be too ambitious to anticipate Africa replicating the Indian vaccine sector’s strategies and mechanisms in every way and detail. Although the two regions share enough similarities regarding disease profiles, geographies, climates, economies, etc., differences in competition, technology, and market dynamics cannot be ignored.

These differences could benefit and challenge the vaccine sector in Africa. The region must prioritize the creation of a resilient, sustainable, and robust life sciences ecosystem that will support the pharma, medical technologies, and vaccine sectors in the long run.

Development of a strong life sciences ecosystem that nurtures the overall vaccine sector

Africa needs to form close ties with multiple supporting networks, similar to how the Indian vaccine producers networked with the local biosciences ecosystem. These supporting networks must be associated with the production of multiple pharmaceutical products for a region, building a strong scientific labor force alongside reinforcing its regulatory system.

Higher level of autonomy for the leadership teams of government-led vaccine facilities

One of the key learnings from the pitfalls of India’s vaccine sector is that the executive/leadership teams of government-owned vaccine facilities should receive a higher level of autonomy. Interferences from government agencies should be avoided to the maximum extent possible. A classic example from the Indian market is the 2020-2021 downfall of HLL Biotech Limited which could not produce any COVID-19 vaccine owing to government interferences in the technology upgrade and production-related decisions.

EOS Perspective

For the African vaccine development and production industry to embark on a path of growth, it is imperative to learn from the valuable lessons available. However, with limited financial resources and insufficient infrastructure, it is crucial to prioritize the actions taken to ensure maximum progress.

To start building a favorable environment, it might be beneficial for the African markets to develop policies emphasizing process patents more than product patents, at least in the initial few years. This could be akin to regulations in the Indian pharma sector of 1970-1995, which proved quite effective and could fuel the growth of the generics market in Africa. Creating such an environment would waive off patent protection of branded drug manufacturers initially so that the local pharma companies can produce medicines at a low cost without paying royalties for copying the drug formulations of the branded drugs. Therefore, Africa can focus on building their generics market first and utilize the profits from there to reinforce the vaccine industry.

Secondly, African governments should initiate expanding the number of technology transfer hubs across the continent that focus not only on mRNA-based vaccines but also on newer DNA-based vaccines that are more suited for the African climate. Partnerships and collaborations with research institutes that are already working towards this goal can be a good first step.

One crucial step, which should not be delayed, is building a robust, skilled workforce to drive the sector development. Unfortunately, most African countries’ current education curricula are not in sync with the continent’s needs for vaccine manufacturing. Therefore, Africa urgently needs investment in education from various sources to develop the backbone of the vaccine industry so that the new education system can produce employable graduates in this field. It is important to note that the African governments should take a significant portion of this responsibility.

To begin with, new graduates can be something other than tertiary-educated, highly specialized professionals, such as PhDs. Rather than that, some form of vocational training in vaccine manufacturing or bachelor’s programs in relevant subjects, such as pharmacy, chemistry, etc., would help produce sufficiently skilled labor. This manpower can work and train further on the job under the guidance and supervision of foreign high-level talent and local high-level scientists who are present in the continent relatively sparsely.

These vocational programs should be designed in a collaborative effort between educational institutions and the existing and new vaccine manufacturing facilities in Africa. This would increase the chances of the African manufacturing facilities absorbing the graduating trainees.

India’s education evolution demonstrates the significance of having domestically bred relevant talent to augment and strengthen its own pharma and vaccine sector. This can empower Africa to curb the costs associated with foreign talent hunting and be more resilient to situations such as staff shortages, foreign staff availability fluctuations, etc.

Moreover, it is the responsibility of African governments to support the creation of jobs in vaccine manufacturing and R&D to attract the newly-trained workforce. A proven approach to this is to offer incentives for employing local talent to foreign and domestic investors who intend to set up vaccine facilities in the region. The incentives could range from tax rebates, exemptions, or credits, to offering employee training grants, subsidies for insurance coverage, etc. If this can encourage the creation of jobs in the sectors, young Africans will likely be keen on enrolling in related vocational programs.

Looking at the long-term objectives for the continent’s vaccine industry path, Africa’s primary aim should be to meet its own domestic vaccine needs in terms of both volume and disease spectrum.

Africa can learn critical lessons from India’s strengths and weaknesses in the vaccine sector. The weight of kick-starting the industry development inevitably lies on the African governments’ shoulders, and the sector will not develop on its own. It is high time for stakeholders, such as state governments, regulatory bodies, institutes, pan-African organizations, and local pharma companies, to speed up the process of absorbing and implementing these lessons. It is the only way to achieve the goal of 60% domestic vaccine production by 2040.

18/07/2024by EOS Intelligence EOS Intelligence No Comments

Why Can India’s Vaccine Success Story Be a Sure Shot Template for Africa?

Africa is currently facing significant challenges related to limited accessibility to vaccines as well as ongoing vaccine hesitancy. African CDC has identified these problems and is taking concrete steps to achieve its 2040 target of 60% of vaccines available on the continent to originate from domestic production. India is one of the key countries invested in the growth of Africa’s healthcare sector both financially and logistically. Due to similar geographies, climates, disease prevalence, and economies, Africa could take guidance, collaborate, or replicate Indian vaccine manufacturers’ strategies and mechanisms to scale up its vaccine sector.

Africa has one of the lowest average vaccine administration rates globally

Unbalanced access to vaccines in Africa compared to other regions became quite vivid during the COVID-19 pandemic. Africa’s average number of coronavirus vaccine doses administered per 100 people was 54.37 as of March 15, 2023. Seychelles administered the highest number of vaccine doses at 205.37 and Burundi the lowest at 0.27.

In contrast, the world average stood at 173, with high-income countries such as the USA and Canada administering 191 and 258 vaccine doses per 100 people, respectively. Interestingly, Cuba, despite being an upper middle-income economy, administered 385, a higher number of doses per 100 people than some high-income countries.

Even some low-income economies such as Vietnam (276), Bhutan (264), Bangladesh (218), Nepal (213), and Sri Lanka (184), among others, administered a higher number of coronavirus vaccine doses than the world average (173), and far more than Africa’s average.

These stark variations in the vaccine administration rates across countries could be attributed to the lack of easy accessibility, especially in Africa, apart from other factors such as vaccine hesitancy.

Africans’ vaccine hesitancy slows down the uptake of vaccination

Vaccine hesitancy is caused by several factors such as personal beliefs, misinformation or myths, healthcare infrastructure and access, religious and cultural beliefs, and vaccine safety concerns. These are typically the main reasons for vaccine hesitancy according to an October 2023 article published by ThinkGlobalHealth, and several of these reasons are likely to apply to the African continent.

In addition to these, another critical factor that cannot be ignored is people’s lack of trust in the health ministries, a relevant aspect in some African countries such as South Africa. This was largely due to the ministries’ involvement in procurement corruption of COVID-related aid according to an article published by GlobalData in November 2023.

Africa’s low vaccine administration rate is driven by limited accessibility

One major reason for the vaccine’s low administration rate in Africa is the limited accessibility to vaccines. This has been an ongoing issue on the continent and was not just limited to pandemics such as COVID-19 and Ebola.

The African continent is overdependent on vaccine imports, with 99% of its vaccine needs being satisfied from abroad. With a total of 13 operational production facilities across the continent, the current vaccine manufacturing industry is in its infancy in Africa and produces 1% of the continent’s vaccine supplies.

African countries have recognized this issue and begun working towards its goal of meeting 60% of the continent’s vaccine needs domestically by 2040, with interim targets of 10% by 2025 and 30% by 2030.

This article is part of EOS' Perspectives series on vaccines landscape in Africa. 
Read our other Perspectives in the series:

Vaccines in Africa: Pursuit of Reducing Over-Dependence on Imports

With some local talent available, Africa needs the right development template

While the local vaccine industry is underdeveloped, to say the least, the continent is not entirely without the talent required to produce home-grown vaccines and other pharmaceutical products such as test kits. For instance, Senegal-based Pasteur Institute developed a US$1 finger-prick at-home antigen test for COVID-19 in partnership with Mologic, a UK-based biotech company. Although the funding came partially from the UK, local talent was predominantly utilized.

To establish a sustainable vaccine sector, Africa does not need to reinvent the wheel. It could utilize lessons and success stories of other countries that have built this industry and share similarities with the African continent.

India is one such country with a vast size, diverse cultures, geography, and administrative structures under one roof, and has a tropical climate and disease profile similar to those in Africa. Additionally, India’s symbiotic relationship with the African healthcare sector would also play a significant role in empowering Africa to leverage the expertise of the Indian vaccine sector. This could be a step in the right direction for the African continent to achieve vaccine sovereignty.

Why Can India’s Vaccine Success Story Be a Sure Shot Template for Africa by EOS Intelligence

Africa’s partnership with India in healthcare is not new

Africa has a long-standing healthcare partnership with India, as the latter has been the largest supplier of generic medicines to Africa. Additionally, some US$3.4 billion worth of pharma products, i.e. close to 20% of India’s total pharma exports, went to African countries as of 2018. In 2020-2021, India’s pharma exports to Africa amounted to US$4.3 billion as per the Pharmaceuticals Export Promotion Council of India (Pharmexcil).

Between 2010 and 2019, India was also the third-largest contributor to Africa’s healthcare investment landscape, after the UK and the USA. During this period, India invested around US$210 million out of a total of US$1.1 billion in global investments into Africa’s healthcare sector, accounting for a 19% share.

In the past, African pharma companies have relied on Indian organizations to pivot and streamline their business in difficult times. For instance, South Africa-based Aspen Pharmacare could not sell a single dose of its COVID-19 vector vaccine owing to multiple factors, such as the rising popularity of mRNA vaccines. Ultimately, the company partnered with the Serum Institute of India (SII) in August 2022 to produce its vaccines to minimize business loss and idle production capacity. This is just one example showcasing opportunities where African vaccine producers collaborated with Indian vaccine makers. This kind of collaboration can also become a source of guidance and knowledge on how to create own sustainable ecosystem for vaccine production.

Collaborations between Africa and India have also extended beyond adverse situations. One example of this is a partnered research to produce a DNA-based dengue vaccine. Scientists from Bangalore and Goa in India and Nairobi and Cameroon in Africa have been working together in a partnership called the India-Africa Health Sciences Collaborative Platform (IAHSP), set up in 2019. The partnership results from a collaboration between India’s ICMR (Indian Council of Medical Research) and the African Union to create this DNA-based dengue vaccine, among other research work involving antimicrobial resistance, per a January 2022 Springer Nature article.

Furthermore, in December 2020, the Indian Healthcare Federation (NATHEALTH) and the African Health Federation (AHF) partnered to foster investment in healthcare and thus promote business opportunities in healthcare between India and Africa.

India’s pharma industry has merits to learn from

The Indian vaccine production sector is rapidly gaining steam in the global market and outpacing multinational players in this industry. A few prominent Indian vaccine producers, such as SII, Bharat Biotech (BBIL), and Biological E, have captured a considerable market share globally.

Interestingly, over 60% of the global vaccine needs in terms of volume are being satisfied by only five producers globally. Three of these five producers are based in India: Pune-based SII, Hyderabad-based BBIL, and Mumbai-based Haffkine. SII tops the list of these five global producers with a 28% volume share globally, and BBIL (9%) shares the third spot with Sanofi, followed by Haffkine (7%), as of 2019.

For many years, India has been supplying cost-effective and high-quality generic medicines and vaccines, which has earned the country the title of ‘pharmacy to the world’. The title is not exaggerated, as India alone accounts for 62% of global vaccines and 20% of global generic drugs’ production by volume as of 2023. The Indian pharma sector holds the third rank by production volume and tenth by value globally.

With an 18% share of pharmaceutical exports and vast needs, Africa is the second-largest importer of pharmaceutical products from India as of 2019.

Indian vaccines’ success in Africa proves that Indian producers understand African needs

In its quest to develop its own vaccine production sector, Africa can learn a host of aspects of vaccine production from India. This includes but is not limited to the cost-effectiveness of vaccines against diseases such as COVID-19, rabies, diphtheria, pertussis, tetanus (DPT), human papillomavirus (HPV), malaria, Ebola, and meningitis. India is four to five decades ahead of Africa in vaccine manufacturing and has already done its homework on how to do it right. That’s a useful source of knowledge for Africa’s budding industry, especially since Indian-made pharma products tend to align well with the needs of the African continent.

Serum Institute of India’s (SII) foothold in Africa

SII is now the largest vaccine producer by the number of doses manufactured and sold worldwide (over 1.6 billion doses across 170 countries in 2020), including for polio, diphtheria, tetanus, pertussis, haemophilus influenzae type b (Hib), BCG, r-Hepatitis B, measles, mumps, rubella, as well as pneumococcal and COVID-19 vaccines. According to estimates, nearly 65% of children across the globe receive at least one vaccine produced by SII.

SII has a strong foothold in Africa, with several of its vaccine products being extensively used or developed specifically for the continent’s needs.

MenAfriVac, manufactured by SII, is a vaccine to prevent meningitis and was rolled out in Africa in 2010. The vaccine was developed specifically to curb the spread of meningitis in Africa to cater to the vaccine needs of its population. The price of the vaccine is less than US$0.50 per dose, with an efficacy of 52% among 12–23-month-old children and 70% among older children and adults. Thanks to the vaccine, over 152 million people were inoculated by MenAfriVac by the end of 2013, enabling the elimination of meningitis epidemics in 26 African countries.

Another example of an India-made vaccine to particularly reduce Africa’s disease burden of malaria and cater to its people’s vaccine needs is R21/Matrix-M. SII, along with Oxford University, has produced this malaria vaccine using the technology of Novavax, a US-based biotech company. The vaccine has been approved for use by some African countries’ regulatory authorities, such as Ghana, Nigeria, and Burkina Faso, as of December 2023. According to a January 2024 press release by SII, the vaccine showed efficacy of around 78% in the age group between five- and seventeen-months children in Burkina Faso, Kenya, Mali, and Tanzania over the first year. The company is planning to roll out the 25 million vaccines produced in the coming four to five months.

In December 2022, SII acted rapidly on the Sudan Ebolavirus outbreak in Uganda by sending over 40,000 doses of the investigational ChAdOx1 SUDV vaccine in a record time of 80 days after WHO declared the epidemic.

These are some examples showcasing the fact that SII, along with other Indian producers, understands Africa’s vaccine needs, which is evident from the success of these vaccines in Africa. Consequently, it makes logical and economic sense for Africa to learn from Indian vaccine manufacturers to develop low-cost, effective vaccines.

Apart from successfully selling its vaccines in Africa, SII also actively contributes to the knowledge transfer into the continent. In January 2024, SII partnered with the Coalition for Epidemic Preparedness Innovations (CEPI) to foster low-cost vaccine production in Global South countries, including Africa (also comprising Latin America and the Caribbean, Asia (excluding Israel, Japan, and South Korea), and Oceania (excluding Australia and New Zealand)) to curb the outbreak of life-threatening diseases. CEPI is a global organization formed as a result of an international collaboration between public, private, philanthropic institutions and NGOs.

CEPI has three other members apart from SII: South Africa-based Aspen Pharmacare, Senegal-based Institut Pasteur de Dakar, and Indonesia-based Bio Farma. With this partnership, CEPI intends to capitalize on SII’s expertise in making affordable, cost-effective vaccines in record time. In this pursuit, CEPI is investing US$30 million so that vaccine developers who are already partners of CEPI can expedite technology transfers to SII within days or weeks of any outbreak. This will enable SII to produce vaccines against the impending disease.

Bharat Biotech’s (BBIL) foothold in Africa

With over 145 global patents and a portfolio comprising over 16 vaccines, BBIL has sent over 6 billion doses of vaccines to 125 countries worldwide. BBIL has produced vaccines against influenza H1N1, rotavirus, Japanese encephalitis (JENVAC), rabies, chikungunya, zika virus, and cholera. The company is also the creator of the world’s first tetanus toxoid conjugated vaccine for typhoid. In addition to these, BBIL has manufactured WHO pre-qualified vaccines, such as BIOPOLIO, ROTAVAC, ROTAVAC 5D, and Typbar TCV against polio, rotavirus, and typhoid infections, respectively.

BBIL has also been offering its products to Africa. In one of the recent examples, the company delivered its rotavirus oral vaccine, ROTAVAC, to Nigeria to immunize the country’s children in August 2022. The vaccine is expected to minimize the occurrence of the disease and death due to rotavirus among Nigerian children below the age of five years by at least 40%, according to research by the Johns Hopkins Bloomberg School of Public Health.

Another example of a vaccine made by BBIL that is aligned with the needs of the African population is MTBVAC. In March 2022, the company announced its partnership with Spain-based biopharmaceutical company Biofabri to develop, produce, and distribute MTBVAC, a novel TB vaccine. Phase 3 trial is currently underway in TB-affected regions of Sub-Saharan Africa such as South Africa, Madagascar, and Senegal. With 25% each, Sub-Saharan Africa and India account for the highest TB burden across the globe. The vaccine is being developed to target TB in these susceptible regions to eradicate the disease.

Several other Indian manufacturers have rolled out successful vaccines against various diseases in Africa that have significantly reduced the disease burden in the region.

EOS Perspective

Achieving 60% local vaccine production within 15 years will be possible only if Africa chooses a robust role model to learn from. India stands out as possibly the only near-perfect choice for that. To foster the development of a seamless and sustainable vaccine ecosystem, Africa should replicate, take guidance, and collaborate with Indian manufacturers as much as possible.

The world has evolved and many steps taken by India in the past cannot be directly transplanted into the current African scenario. However, India’s approach to building self-reliance in pharmaceutical production can undoubtedly offer valuable lessons. Direct know-how and technology transfer, collaborations, approach to talent training, production facilities management, procurement handling, supply chain management, licensing, and IP protection are critical aspects in which Africa could utilize India’s expertise and experience in vaccine making.

By choosing India as a role model and emulating its focus on nurturing a competitive pharma manufacturing industry, Africa could take a significant step towards achieving the goal of self-sufficient vaccine production.

20/06/2024by EOS Intelligence EOS Intelligence No Comments

IRA: Are Patients Winning at the Cost of the US Pharma Sectoral Growth?

The market reaction to the US Inflation Reduction Act of 2022 is mostly mixed. It is expected to change the pharma industry dynamics in terms of the competitive positioning and product pricing of those companies projected to be negatively impacted by the IRA. The answer to whether the IRA will be able to curb rising healthcare costs in the USA lies in the legislation’s on-the-ground application.

IRA to decrease prescription drug prices via a four-pronged strategy

Prices of prescription drugs in the USA are 2.78 times higher than in 33 other countries analyzed in a 2024 report published by RAND, a public policy think tank.

In pursuit of reducing healthcare costs in the USA, the Biden government passed the Inflation Reduction Act (IRA) in August 2022. One of the major goals of the act includes the reduction of prices of prescription drugs.

This is expected to be achieved through a four-pronged strategy, the mainstay of which involves the US federal government negotiating the prices of some high-priced prescription drugs covered under Medicare.

The second prong includes pharmaceutical firms paying a rebate to Medicare if they raise the price of prescription medicines covered under Medicare by a rate that is higher than the inflation rate.

The monthly cost of insulin for Medicare patients is capped at US$35, as the third prong.

The fourth prong aims to reduce prescription drug prices by capping the out-of-pocket costs of Medicare Part D patients at US$4,000 in 2024 and US$2,000 in 2025.

IRA Are Patients Winning at the Cost of the US Pharma Sectoral Growth by EOS Intelligence

Pharma companies to suffer more due to IRA compared to projected government savings

Under the IRA, large pharmaceutical companies, defined as those with over US$1 billion in net profits, are required to pay a minimum of 15% annual taxes, a financial burden on these companies. Analysts predict that the annual revenue from corporate taxes could be to the tune of US$222 billion. Furthermore, the IRA is expected to save over US$287 billion for ten years from the roll-out, as per the estimates of the Congressional Budget Office (CBO).

Apart from the increased financial burden on some companies, experts foresee potential adverse impact on several pharmaceutical companies based in the USA to a considerable extent.

The pharma companies witnessing the least to no impact are the ones with their primary operations based outside the USA, biologics or large molecule drug producers, and the ones that do not receive government funding for R&D. This is because of the differing timelines under IRA for negotiating the prices of biologics and small molecules. Biologics’ timeline is 11 years after FDA approval, while small molecule drugs are eligible after 7 years. Therefore, Medicare negotiations will begin four years earlier for a small molecule drug that has received approval at the same time as a large molecule biologic drug.

Apart from these adverse effects, such as differential treatment of small molecule drugs compared to biologics under Medicare price negotiation timelines, there are some other negative impacts on the overall US pharma industry, such as diminishing competition among generic drug producers, decreased discovery of new treatments, and new uses of existing drugs.

IRA to affect the revenues of top pharma companies surely but variably

There are differing viewpoints regarding the impact of IRA on pharmaceutical companies’ revenue. One group of experts suggests that Medicare prescription drug negotiations under the IRA will depend on the expiration of the drug’s patent. Other experts expressed their opinion that irrespective of when a drug loses exclusivity, a significant threat to drug revenues comes from the competition entering the market and not from lower negotiated drug prices.

The first group of experts states that lower negotiated prices in 2026 are expected to have a lower impact on medicines projected to witness revenue loss owing to patent expiry around the same time. One such example of a drug losing its exclusivity in the USA in 2025 is Stelara by Janssen Biotech approved for treating psoriasis.

In contrast, pharma companies producing medicines that are expected to witness competition from their generic counterparts after 2026 are projected to lose revenue owing to lower negotiated prices even before the drugs lose exclusivity. However, some companies’ revenue will be affected more than others.

Medicare price negotiations to hit revenues of some drugmakers drastically

The pharma industry’s revenue is expected to decrease by 2% due to the new measures brought about by the IRA, as per a 2022 report by Morningstar, a US financial services firm. Among the companies that will be highly affected are Novo Nordisk, Gilead, Bristol Myers Squibb, AbbVie, and AstraZeneca. In contrast, others, such as Pfizer, Merck, Roche, and Novartis, will not be as much impacted by Medicare price negotiations.

Some 15% of global branded drug sales come from Medicare in the USA, as per Morningstar estimates. Therefore, the impact of the IRA on pharmaceutical companies depends on their reliance on Medicare sales, price adjustments, high-cost specialized drugs, and extended patent protection.

Medicare prescription drug negotiations are projected to impact pharma companies the most among all IRA measures, although this impact might not be uniform across the players. On the other hand, Medicare negotiations are projected to save the government approximately US$100 billion through 2031. The pharma companies facing the highest revenue losses include Novo Nordisk, Gilead, and AstraZeneca.

When the Medicare price negotiation measures start to roll out in 2026, two drugs of Novo Nordisk, namely, Ozempic and Rybelsus, that are approved to treat type 2 diabetes, are expected to witness an 8% decline in their projected revenue through 2031, as per Morningstar. Gilead’s Biktarvy, which treats HIV-1 infections, is expected to be subject to price negotiation in 2027 and thereby face a projected revenue loss of 7% through 2031. On similar lines, Calquence (to treat mantle cell lymphoma) and Tagrisso (to treat non-small cell lung cancer) drugs of AstraZeneca are expected to lose 6% revenues through 2031 owing to Medicare price negotiations.

In contrast, considering the existing portfolios, Pfizer, Merck, Bristol Myers, and BioMarin are expected to witness no revenue loss due to Medicare negotiations.

Medicare inflation caps to impact major pharma companies negatively

Another important IRA measure is Medicare inflation caps. This measure involves drug producers paying penalties for increasing drug prices beyond the inflation rate. It is expected to result in US$62 billion in government savings through 2031.

Around March 2023, the US federal government, along with the Centers for Medicare & Medicaid Services (CMS), released a list of 27 drugs whose prices were increased by their manufacturers at a higher rate than the inflation rate. This list included AbbVie’s Humira (to treat Crohn’s Disease) and Astellas Pharma’s and Seagen’s Padcev (to treat urothelial cancer). Gilead Sciences, Johnson & Johnson, and Pfizer are among other impacted companies by Medicare inflation caps. Pfizer had the most drugs on the list, with a total of five.

Bristol Myers Squibb is one of the pharma companies that is expected to be highly impacted by Medicare inflation caps. The company’s drugs, such as Eliquis (to treat or prevent blood clots), Opdivo (to treat melanoma), Orencia (to treat rheumatoid arthritis), and Yervoy (to treat various cancer types) are among the medicines that are expected to face revenue loss owing to inflation caps. Other drugs on the list include Novo Nordisk’s drugs such as Novolog and Levemir (both for type 1 diabetes) and Victoza (for type 2 diabetes), Johnson & Johnson’s drugs such as Imbruvica (to treat certain cancers) and Xarelto (to treat or prevent blood clots), along with Novartis’s Sandostatin (for severe diarrhea and flushing related to metastatic carcinoid tumors).

In contrast, Merck is not expected to face any revenue loss due to inflation caps, while GSK, Regeneron, Roche, and Sanofi are projected to witness minimal revenue loss as these companies have not raised the prices of their drugs beyond the inflation rate.

IRA to potentially reduce competition from generics

According to the IRA, following the price negotiations of some of the branded drugs, manufacturers of the generic versions of such drugs will have less scope to charge a reduced price for those drugs. This would disincentivize the generic drug producers to manufacture generic versions of the already low-priced branded drugs.

EOS Perspective

The IRA represents a substantial change in the US legislation that strives to make healthcare more affordable to Americans through increased access to more reasonably priced prescription medicines.

However, IRA can be expected to affect small-molecule drugmakers more negatively than biologics. Moreover, some pharmaceutical companies are projected to feel the pinch more than others in terms of revenue losses.

Companies such as Merck, Bristol Myers Squibb, and the pharmaceutical association PhRMA have filed lawsuits against some provisions of the IRA, stating that they are unconstitutional. Bristol Myers Squibb and J&J are planning to appeal after the US court dismissed the IRA lawsuits. These pharmaceutical companies are trying to find ways to circumvent the negative impact of the legislation.

IRA is also expected to negatively impact R&D and medical innovation. This is evident from the fact that biopharma companies have reduced their R&D efforts in the neuroscience space, especially since a lot of development work in this space involves small-molecule drugs. Moreover, as IRA exempts only one orphan drug from price negotiation, investments in R&D for orphan drugs are likely to get deprioritized. Many pharmaceutical companies are reconsidering their R&D planning and investment strategies to counter the effect of IRA.

IRA is clearly not a win-win strategy for all stakeholders. Pharmaceutical companies are mostly at the losing end, while patients could be winners. Considering all the positives and negatives of IRA, only time will tell the actual impact of the legislation on the overall pharmaceutical industry.

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IRA to potentially reduce competition from generics

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