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Recall Aftermath Who is Gaining Share in the Sleep Apnea Devices by EOS Intelligence
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Recall Aftermath: Who is Gaining Share in the Sleep Apnea Devices and Ventilators Market?

In recent years, the number of ventilator recalls has increased considerably, primarily due to product quality issues, software malfunction, and manufacturing defects. This affected manufacturers such as Philips, Medtronic, and Vyaire Medical, leading to brand damage, financial losses, and a shift in the market competition. Existing players and new entrants such as Getinge and Nihon Kohden are stepping in to fill the gap with innovative and non-invasive products. The recalls caused challenges for manufacturers and patients, highlighting the need for strong quality control and regulatory oversight.

Recalls of its sleep apnea devices and ventilators hit Philips the hardest

The medical device industry has recently experienced many product recalls, particularly in the ventilators segment, impacting major market players such as Philips, Medtronic, Baxter, GE Healthcare, Hamilton Medical, and Vyaire Medical.

Philips (Philips Respironics) faced a series of class I respiratory product recalls, including CPAP and BiPAP machines, and ventilators, due to health risks caused by the polyester-based polyurethane (PE-PUR) sound abatement foam breakdown in the devices. Industry experts consider Philips’ sleep apnea devices and ventilator recalls among the most significant since 2021. As of January 2024, the company experienced a recall of over 15 million sleep apnea devices and ventilators, and reportedly hundreds of deaths. The recall seriously hurt the company’s reputation, weakened its position in the market, and caused significant financial problems.

The recalls led to a decline in the company’s share price by 60-70% in 2021, and it is still about 50% lower than its peak in April 2021 (US$ 53.45). Comparable sales of the connected care segment, including sleep apnea devices and ventilators, declined by about 19% in 2021 in comparison to 2020. This happened primarily due to sleep apnea devices and ventilators recalls, and the normalization of demand for hospital ventilators and monitoring systems following the COVID-19 surge. Recalls continued to drive down ventilator and sleep apnea device sales in 2022 and 2023.

The considerable impact on sleep apnea devices and ventilator sales resulted in a decline in Philip’s share in the sleep apnea device market, dropping to an estimated 20% between 2021-2023 from over 30% before the recall. The company also experienced a notable decline in market share in the ventilators market. Despite the decline in market share, Philips maintained its position as one of the leading players in both the sleep apnea devices and ventilators market.

However, in January 2024, Philips agreed to halt the sales of 19 sleep and respiratory products in the USA as a part of the consent decree with the US Department of Justice (DOJ). These products included hospital ventilation, certain home ventilation, sleep diagnostic devices, and portable and stationary oxygen concentrators. This affected the company’s brand image greatly and resulted in a further loss of market share in both ventilators and sleep apnea devices markets. Since the company will continue to sell consumables and accessories, including masks, it is anticipated to maintain a portion of its market share in both segments.

In April 2024, the company agreed to pay US$1.1 billion in legal settlement to resolve injury-related cases caused by sleep apnea devices and ventilators in the USA. Overall, sleep apnea device recalls cost the company over US$5 billion, likely including charges such as provisions for Philips Respironics-related litigation, consent decree, remediation costs, legal settlements, workforce restructuring, and quality remediation action. In addition, Philips cut 6,600 jobs by 2023 and is likely to reduce its workforce by a total of 10,000 by 2025.

Several companies bore the brunt of their own ventilator recall setbacks

Other prominent manufacturers such as Drägerwerk (Draeger), Medtronic, Vyaire Medical, Hamilton Medical, and Baxter also experienced various ventilator recalls due to manufacturing and quality defects. Although the FDA classified these recalls as serious, these companies did not face the same severe consequences as Philips, as these recalls did not result in major injuries.

All these manufacturers also witnessed a drop in ventilator sales largely due to the stabilization of demand for ventilators following the COVID-19 surge, with product recalls also contributing to the downturn.

In February 2024, Medtronic completely exited the ventilator market due to unprofitability. Similarly, in June 2024, Vyaire Medical filed for bankruptcy and was subsequently acquired in October 2024 by Zoll, an Asahi Kasei company engaged in the manufacturing of medical devices and related software solutions. This caused a profound impact on the ventilators market.

Market players are introducing products with advanced features to gain market share

The ventilator market encountered a radical shift in competition due to numerous product recalls. The suspension of sleep and respiratory product sales cost Philips its leading market position in sleep apnea devices and ventilators (except for certain home ventilators). It remains unclear when or if Philips will be able to resume sales of these devices. However, the company is unlikely to leave its presence in the sleep apnea devices and ventilators market entirely due to its commitment to service and supply of parts of ventilators in use, as well as its decision to continue the sale of consumables and accessories.

Existing market players such as Getinge, Hamilton Medical, Drägerwerk (Draeger), ResMed, and GE Healthcare, and newer entrants such as Nihon Kohden, are likely to fill in the gap left by Philips, Medtronic, and Vyaire Medical in the USA.

Market players such as Getinge, Drägerwerk (Draeger), and Nihon Kohden are focusing on introducing technologically advanced ventilators with features such as enhanced patient comfort, advanced monitoring capabilities, portability, and adaptive ventilation modes, to grab a slice of the pie. They are also increasingly focusing on expanding their portfolio of non-invasive ventilators with different interfaces, including face masks, nasal masks, helmets, and mouthpieces.

For instance, in October 2024, Nihon Kohden introduced a new ventilator system that combines invasive and non-invasive ventilation and high-flow oxygen therapy in one device, offering adaptability and eliminating the need to switch between machines. It also features a customizable, app-based touchscreen interface with advanced monitoring capabilities. Similarly, in January 2024, Getinge introduced ‘Servo-air Lite’, a non-invasive ventilator with high-flow therapy that offers optimal respiratory support, enhanced patient comfort, and ease of use for clinicians.

ResMed, a leading player in both the sleep apnea devices and ventilators market, is estimated to have grabbed over 10% of Philips’ market share in the sleep apnea devices market in the USA. ResMed witnessed a substantial increase in demand for its sleep and respiratory care products, including sleep apnea devices and ventilators, for various reasons, including Philips’ product recalls. The demand for its sleep and respiratory care products in the USA, Canada, and Latin America increased by 16%, 25%, and 10% in 2022, 2023, and 2024, respectively.

Companies engaging in sleep apnea devices and ventilator rentals, sales, and distribution, such as Trace Medical, also started adding brands from different companies to their product mix to meet the demand for these devices.

Patients experience delays in treatment and struggle to switch to other brands

Philips’ foam degradation issue has exposed patients to severe health risks, leading to respiratory complications and even cancer. Recalls of many ventilators and sleep apnea devices have left hospitals struggling to replace them, causing delays in patient treatment.

Patients relying on a specific brand faced reduced treatment options. Many patients found it difficult to switch to other brands due to cost and differences in machine settings or interfaces. With Philips halting sales of various sleep apnea devices and ventilators, patients have no choice but to switch to other brands.

The recall of various products from different companies has created significant demand and supply chain pressures for existing companies. These pressures will likely drive up ventilator and sleep apnea device prices, further burdening patients.

EOS Perspective

Product recalls in the sleep apnea devices and ventilator segment brought quality issues to the limelight. This highlights the need for stronger quality control processes and technologically advanced sleep apnea devices and ventilators incorporating virtual monitoring and AI integration, which can help detect defects earlier.

While the FDA received complaints about Philips’ degradation of the sound abatement foam in the sleep apnea devices and ventilators before the recall initiation, decisive action to force correction was not taken immediately. Also, despite knowing that Philips had been aware of the foam degradation issue for many years, the FDA did not take stronger enforcement measures against the company sooner. This situation highlights the importance of assessing and enhancing the FDA’s oversight process to ensure timely response to medical device complaints.

Philips suffered lasting brand damage due to the recalls. Although the company is trying to regain shareholder and consumer trust after settling US claims for an amount much lower than anticipated (US$2-5 billion) by analysts and the public, it faces a long road ahead.

Regarding market competition, ResMed is estimated to continue to lead and strengthen its dominant position in the sleep apnea devices market. The exit of well-established players from the ventilator market will intensify competition among existing companies and new entrants seeking to capture market share. However, it will be a gradual process as customers slowly transition from existing products to new brand ones. On top of that, the new entrants are likely to face stricter regulatory norms and product approval processes aimed at reducing the number of product recalls and enhancing patients’ safety.

DeepSeek’s Disruption Reshaping the Global AI Battlefield by EOS Intelligence
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DeepSeek’s Disruption: Reshaping the Global AI Battlefield

In January 2025, DeepSeek AI introduced two powerful large language models (LLMs) that shook the AI world. Developed at a fraction of the cost of its existing peers, DeepSeek holds the potential to transform the AI development landscape globally.

DeepSeek’s efficiency enables better cost-effectiveness by reducing computational needs

DeepSeek’s V3 and R1 models focus on efficiency and require less computing power than rival models while delivering equivalent performance. Its efficiency stems from using the “Mixture-of-Experts” (MoE) architecture, which activates only parts of the model for a given task, minimizing computational needs. This targeted use of computational memory reduces operational costs, giving it a significant edge over competitors who rely on more resource-intensive approaches.

The arrival of DeepSeek has sent shockwaves throughout the US tech industry, marked by a significant decline in stock values. The key headline event was Nvidia’s US$600 billion drop in market capitalization. The fact that a Chinese company was able to achieve groundbreaking results at a fraction of the cost by using low-power Nvidia H800 chips challenges the investment poured into the market by established players.

The open-source model enables widespread applications at a budget

DeepSeek has embraced a fully open-source model, allowing anyone to utilize their technology for commercial purposes. DeepSeek’s open-source approach democratizes access to AI, enabling a wider range of applications.

The availability of DeepSeek’s advanced APIs at a very low cost also appeals to customers who have previously been priced out of advanced AI applications due to the higher costs of proprietary LLM models such as OpenAI’s GPT.

The AI ecosystem already feels the impact of DeepSeek’s triumph. Its free AI assistant has also made a significant splash in the consumer market, with DeepSeek’s app surpassing ChatGPT in Apple Store charts. Its cost-effectiveness has even attracted the attention of major players such as AWS and Snowflake, which are now offering DeepSeek’s technology on their platforms.

Following DeepSeek’s success, several other Chinese companies may follow suit by developing more efficient yet high-performing AI models, further driving the costs down. Alibaba already released a new version of its Qwen 2.5 model at the end of January 2025.

Initial success of DeepSeek does not guarantee dominance

DeepSeek’s success does not guarantee its dominance in the AI landscape. We have had precedence of a similar company making headway and then falling off in the AI space. Mistral’s open-source AI model, Mixtral 8x7b, initially seemed poised to disrupt the field. However, it quickly fell off the radar when other closed-source models incorporated Mixtral’s innovations.

DeepSeek’s continued success will depend on whether it is able to maintain its edge through continuous innovation, particularly with limited access to high-performance chips.

Read our related Perspective:
 NVIDIA’s Meteoric Rise: Can the AI Chip Giant Sustain Its Dominance?

EOS Perspective

DeepSeek’s emergence as a serious contender has intensified the global AI race, challenging the dominance of established players such as OpenAI, Meta, and Google.

DeepSeek-R1, with its open-source foundation, has already demonstrated impressive abilities in handling complex text-based tasks, such as summarizing documents, answering technical questions, and generating codes. Moreover, it offers these capabilities through APIs at a fraction of the cost of its competitors, potentially disrupting the market and driving down prices for AI services.

With DeepSeek’s AI models requiring less computational power and hardware, they will offer significant cost savings for users. Combined with its open-source model, which fosters customization, collaboration, and broader access, DeepSeek is expected to gain traction rapidly. While it is currently limited to text-based queries, its potential is undeniable.

While questions about Chinese government influence and censorship persist, DeepSeek presents a compelling vision of AI disruption. In the short term, we can anticipate lower AI adoption costs and shrinking profit margins for established AI providers. Furthermore, DeepSeek’s emphasis on efficiency could spark a shift in the industry, prioritizing resource optimization over simply increasing computing power. The full scope of DeepSeek’s impact, however, will only unfold over time.

Open Banking Sparking a Wave of Innovation in Financial Services by EOS Intelligence
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Open Banking Sparking a Wave of Innovation in Financial Services

The adoption of open banking is leading to innovation across financial solutions such as account-to-account payments (A2A), personal finance management (PFM) apps, embedded finance, and banking-as-a-service (BaaS) by enabling real-time data-driven insights and personalized financial services. It is paving the way for a more dynamic financial landscape. Open banking has evolved rapidly since the revised Payment Services Directive (PSD2) came into force in Europe. While challenges exist, adopting open banking solutions, aided by introducing regulatory and security measures, holds the potential to revolutionize the financial services sector.

The introduction of APIs transformed banking services

Open banking has emerged as a transformative force, changing how financial data is shared, and services are offered to consumers. It securely provides third-party financial service providers access to consumer’s financial information with their consent through an application programming interface (API). It aims to foster innovation in financial services, encourage healthy competition, and give consumers more control over their banking information. Several banks across countries, including Citi, Barclays, and Deutsche Bank, have started providing access to their APIs.

Regulatory initiatives and consumer demand lead to open banking growth

While open banking has existed for a long time, it gained traction when the PSD2, a European regulation focused on creating a more open, competitive, and secure payment landscape across Europe, came into effect in 2018.

Since then, several countries have introduced open banking regulations to support its adoption. For instance, in the UK, the open banking initiative, led by the Competition and Markets Authority (CMA, the UK’s principal authority responsible for strengthening business competition and preventing anti-competitive activities), became effective in 2018. In addition to the European countries, Australia, New Zealand, Brazil, and South Africa, among others, have introduced regulatory measures to drive the adoption of open banking.

Countries across the globe are adopting various approaches to open banking, including regulatory-led, market-led, and hybrid approaches. While Europe has taken a regulatory-led approach, adopting open banking in the USA, Canada, and China is driven by consumer demand and technological innovations. Consumers prefer to have control and transparency over their financial data. While there are currently no regulatory frameworks for open banking in the USA, the Consumer Financial Protection Bureau (CFPB) has proposed rules to protect consumer data rights, which will aid in facilitating the adoption of open banking.

Several countries, such as India, South Korea, Japan, Hong Kong, Russia, and Singapore, have adopted a hybrid model, including both regulatory and market-led initiatives. These countries do not have mandatory open banking regimes, but policymakers are looking to introduce initiatives to accelerate open banking adoption. For instance, in Singapore, the Monetary Authority of Singapore (MAS) and the Association of Banks have published an API playbook. This publication aims to support data exchange between banks and fintech players.

The growing emphasis on introducing regulatory measures to ensure data security will likely drive the adoption of open banking.

Open Banking Sparking a Wave of Innovation in Financial Services by EOS Intelligence

Open Banking Sparking a Wave of Innovation in Financial Services by EOS Intelligence

Open banking is driving innovation in financial solutions

The adoption of open banking is transforming financial solutions, including A2A payments, variable recurring payments (VRP), PFM apps, BaaS, and embedded finance, by enabling faster, more convenient, secure, and personalized financial services.

A2A payments and VRP

Open banking allows secure access to real-time bank data to third-party providers, enabling process automation, speeding up A2A payment transfers, and providing a better user experience. Increasing adoption of open banking globally is expected to make international A2A payments more viable and secure.

Digital wallet platforms such as Apple Pay, Google Pay, and Stripe are looking to integrate open banking on their platforms to provide enhanced user experience. In September 2023, Apple soft-launched a new iPhone wallet app in the UK integrated with an open banking framework to replace traditional banking apps as the preferred platform for accessing information related to their account balance, spending history, etc.

Open banking also encourages the widespread adoption of variable recurring payments by giving consumers more transaction control and transparency. The use of variable recurring payments is expected to increase across various commercial payment services, such as utility bills, subscriptions, and insurance premiums, in the coming years.

PFM apps

Access to financial data enables PFM apps to share more effective and personalized financial advice with consumers. A real-time snapshot of the overall financial health of the consumers helps them make long-term financial decisions.

BaaS

Banking-as-a-service platforms are likely to develop due to the adoption of open banking, allowing non-banking entities to provide financial services without becoming certified banks. This offers consumers a variety of payment and credit options, as well as more personalized finance solutions, expanding the industry offering.

Integrating BaaS in retail is being explored to improve customer loyalty programs and provide seamless payments. Also, the scope of services is likely to expand rapidly, from offering banking services to individual consumers to small and medium-sized enterprises (SMEs) and large corporations in the near future.

Embedded finance

Open banking has become the driving force behind the rise of embedded finance, enabling businesses and corporate clients to enhance operational efficiency and user experience. While retail and e-commerce platforms are some of the first to adopt embedded finance, the adoption is likely to increase in less digitalized spaces such as real estate as well.

Synergy with AI and blockchain offers scope for advanced innovation and security

Open banking provides a data-rich environment by aggregating data from various financial institutions for AI algorithms to analyze and utilize for decision-making. It is expected to benefit AI algorithms further by incorporating new features such as data categorization and anomaly detection in the coming years.

On the other hand, AI is likely to increase the effectiveness of open banking by analyzing individual consumer data and enabling the offering of personalized services. AI and open banking will likely help financial institutions develop innovative products.

While both AI and open banking complement their financial services, they can lead to data misuse or unauthorized access concerns, highlighting the need for strong regulatory measures to keep up with the evolution of open banking and AI.

Blockchain technology will likely become more common in open banking as it will enhance the security and transparency of financial transactions. It will likely reduce the risk of data breaches and unauthorized access to consumers’ finances. Additionally, it will likely make it easier for consumers to share their data by simplifying the authentication and consent processes.

Open banking services have expanded from basic payment initiation to open finance

The open banking framework has evolved from basic account information and payment initiation services to open finance, including access to data from various accounts, including savings, investments, pensions, insurance, and mortgages.

Countries such as India, South Korea, Australia, and Brazil have moved from open banking to open finance to develop a more connected financial ecosystem. In February 2024, South Korea also introduced two initiatives focused on including business data and providing offline open banking services.

In Europe, the European Commission is also pushing towards open finance by introducing the Financial Data Access (FiDA) regulation, a framework to enable secured sharing and access of financial data.

Open banking will diversify consumer options, with non-financial companies such as telecom providers, e-commerce platforms, and utility companies offering innovative financial products. They will likely enter into partnerships with banks to provide integrated services to consumers, enhancing their offerings and creating an interconnected financial ecosystem.

Lack of standardized APIs affects the open banking adoption

While open banking is gaining traction, specific challenges, such as lack of standardized APIs, integration with legacy systems, privacy compliance, and data security, are affecting its adoption.

The lack of standardization of APIs across financial institutions is the key challenge in adopting open banking. Third-party providers are usually unable to adapt to different APIs and provide seamless data sharing between systems.

Various financial institutions also face difficulty integrating open banking into their legacy systems, making the integration process complex and expensive. Banks must first update their systems by investing in technology upgrades and partnering with fintech solutions providers to overcome integration challenges.

As the adoption of open banking increases, the chances of data breaches might also increase, highlighting the need to protect customer data and compliance with privacy regulations. Banks are looking to adopt measures such as encryption, clear usage policies, and regular audits to protect customer data. The European Union has also put regulations such as the General Data Protection Regulation (GDPR) and the Digital Operational Resilience Act (DORA) in place to protect customer data and improve the digital security of financial institutions. Advanced security measures solutions, including tokenization and dedicated API gateways, can also help safeguard customer data.

Lack of awareness among consumers is another key challenge. Users are often unaware of open banking and are reluctant to share their financial data due to privacy concerns. Initiatives aimed at educating the users about security and regulatory norms related to open banking by banks can help overcome this challenge and drive adoption.

EOS Perspective

The shift to an open banking model can transform the future of digital banking. The key driving factors for the users are the ease and clarity of the interface, which are likely to replace the traditional banking infrastructure and ownership of consumer data.

The expected introduction of PSR1 in 2026 will likely improve competition and consumer protection in the payments market, which will likely drive the adoption of open banking. PSR1 will help enhance fraud prevention, improve consumer rights and protection, standardize payment regulations, and enhance open banking functions.

The introduction of regulatory and security measures and growing awareness about open banking and its benefits are also likely to aid this growth. A phased implementation of open banking will help with greater adoption of open banking by gradually introducing the concept to the consumers and helping them adapt.

Open banking will benefit banks by providing better customer insights, encouraging innovation, and creating an additional revenue stream through API monetization. However, increasing competition from fintech and non-financial institutions entering the market will likely pressure banks to transition to open banking. The shift to open finance will further increase the competition in the industry. We will likely witness banks entering partnerships with fintech players to develop and offer innovative financial services for their consumers.

The financial sector is embracing open banking as a means to offer creative and innovative financial solutions to enrich the user experience. Open banking will likely evolve into a broad ecosystem of connected services, streamlining the consumers’ products, services, and applications into one, providing a seamless experience.

NVIDIA's Meteoric Rise Can the AI Chip Giant Sustain Its Dominance by EOS Intelligence
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NVIDIA’s Meteoric Rise: Can the AI Chip Giant Sustain Its Dominance?

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NVIDIA has grown exponentially in recent years. The company made significant strides as an early entrant into the AI chip market, becoming the sector’s leading company. In July 2024, NVIDIA’s market cap was US$2.9 trillion, registering 137.1% growth over 2023, making it the world’s third most valuable company behind Microsoft and Apple. As AI development continues its upward trajectory, big tech companies are focusing on developing their AI capabilities more than ever, posing a threat to NVIDIA’s dominance in the AI chip market.

Over the past decade, NVIDIA has evolved from a gaming GPUs maker to a leader in AI and data centers. The company’s early venture into the computing space coupled with continuous development of its cutting-edge technology helped the company solidify its position as the pioneer in the fast-growing AI training and inference market.

According to Mizuho Securities, a Japanese investment and securities firm, NVIDIA holds 70-95% of the advanced AI chip market share in 2024. Despite being the leading firm and major shareholder in the booming AI chip market, NVIDIA started to face rising competition and regulatory scrutiny that challenge its dominance.

Regulatory scrutiny poses a threat to NVIDIA’s market strategy and dominance

NVIDIA’s dominance has caught the attention of regulators worldwide, with antitrust investigations underway in the USA, EU, and China.

The acquisition of ARM, a UK-based semiconductor company, was scrutinized by regulators in multiple countries and was terminated in 2022. This was due to competition and control of key technology. Qualcomm, Google, and Microsoft opposed the deal because of concerns over fair access to ARM’s technology and fair industry practices.

This increased scrutiny may limit NVIDIA’s ability to offer products and services and impact its strategic expansion plans and market dominance.

NVIDIA's Meteoric Rise Can the AI Chip Giant Sustain Its Dominance by EOS Intelligence

NVIDIA’s Meteoric Rise Can the AI Chip Giant Sustain Its Dominance by EOS Intelligence

Competitors are increasingly vying for NVIDIA’s AI chip market share

The global AI chip revenue is projected to reach US$33.4 billion in 2024, per the Gartner market report, making it a lucrative space to operate in. Major tech companies are investing in AI chip development to compete and break NVIDIA’s monopoly in the market.

Through partnerships, innovation, integrated solutions, and niche offerings, competitors are shaping a competitive landscape that will continue to democratize and push AI tech forward. As the AI computing industry will see unprecedented growth, NVIDIA’s competitors are positioning themselves to capitalize on the emerging opportunities.

Tech companies are investing heavily in their AI chip development capabilities

The generative AI boom has exposed how much the big tech companies depend on NVIDIA. NVIDIA’s biggest customers (Microsoft, Google, Amazon, and Meta Platform), which account for over 40% of its revenue, are building their own AI chips to reduce their dependency on NVIDIA.

Amazon, through AWS, offers its own AI chips, Inferentia and Tranium, as cost-effective alternatives to NVIDIA’s chips. Google has been using its tensor processing units (TPUs) since 2015 and recently announced its Trillium chip. Microsoft is building its own AI accelerators, Maia and Cobalt, and Meta is building its own AI chips for more efficiency.

Among all competitors, Intel is likely to emerge as a core competitor to NVIDIA in the AI chip market, leveraging its experience in making CPUs and GPUs. Intel is challenging the company’s dominance in the AI processor market with the Gaudi accelerator AI chip, which costs one-third of NVIDIA’s GPUs.

Intel is focusing on edge devices, such as smartphones, that utilize smaller language models (LLMs) as part of its “AI everywhere” strategy.

NVIDIA is dominating the fast-growing cloud data center market. Intel’s approach of not replicating NVIDIA’s business model but leveraging its broader technology portfolio is likely to provide it with a competitive edge and a chance to compete with NVIDIA.

AI processing shift to edge devices challenges NVIDIA’s market share

Another challenge for the company is the shift in AI processing from data centers to edge devices such as laptops, PCs, and phones.

Large companies, including Apple and Qualcomm, are updating their chips to run AI models on these devices with neural processors for privacy and speed. Apple’s latest devices are AI optimized, and Qualcomm’s new PC chip allows laptops to run Microsoft AI services on-device.

For NVIDIA, adapting to this new paradigm will be important in the long run. As edge AI grows in demand, the company must innovate and compete in this fast-changing market to remain ahead of the competitors.

Investor-backed startups are making strides in the AI chip market

Many new entrants and growing companies are also competing in the AI chip market with innovative approaches and niche solutions.

Startups, such as Graphcore, Cerebras Systems, Groq, and SambaNova Systems, are building specialized AI architectures to outperform traditional GPUs in specific AI tasks. These startups are backed by strong venture capital and strategic partnerships, providing them with resources to enhance their R&D capabilities and scale much faster. For instance, Grog, a startup in the AI inference market, secured US$640 million and claims to have developed an AI chip faster than NVIDIA’s at a much lower price.

The surge in capital investment is likely to support startups in developing new AI chip solutions and carve out a niche for customized AI workloads. This way, startups can tap into new customers seeking customized chips for specific solutions.

Amidst the competition, NVIDIA is expected to leverage its early head start in the AI chip business and will likely focus on its core strength of developing advanced chips.

NVIDIA’s strategic investment in startups strengthens its robust ecosystem

NVIDIA has created an ecosystem that makes it hard for competitors and customers to switch away. Key components of this ecosystem include strategic investments in startups, software bundling, and partnerships, creating a robust and interconnected web.

NVIDIA’s venture capital arm, NVentures, plays a crucial role in product innovation by investing in startups across various industries.

In addition to financial support, NVIDIA also offers these startups access to its technology and expertise to foster innovation and accelerate product development. For example, NVIDIA Inception, a global program, supports startups by providing technology and marketing support, connecting them with venture capitalists, and giving them access to the latest technical and financial resources.

Investing in promising startups provides NVIDIA with early access to emerging technologies and potential market disruptors. This enables the company to integrate the next big technologies into its products or develop new products that keep it ahead of the competition. It fuels innovation and creates a network of companies that are dependent on NVIDIA’s technology, making it hard for them to switch to competitors.

NVIDIA’s seamless hardware-software integration provides a competitive edge

Software bundling is another way NVIDIA strengthens its ecosystem. The company often bundles its hardware with proprietary software, making its products better and more functional. This software is frequently optimized for NVIDIA’s hardware, so customers cannot switch to competitors without losing access to this software. The strategy of bundling often leads to better performance and value for customers, making NVIDIA’s products more attractive.

NVIDIA’s software ecosystem, particularly CUDA (Compute Unified Device Architecture), plays a vital role in its dominance. CUDA only works with NVIDIA’s chips, and over 3 million developers use it to do AI experiments and develop applications. NVIDIA also updates its software annually with new AI chip architectures and software. The company’s continuous innovation ensures its hardware and software are always in sync, so customers stay within the NVIDIA ecosystem.

NVIDIA’s strategic partnerships enable tech integration across sectors

NVIDIA has partnered with companies ranging from tech giants to startups and helps them develop and optimize their software for their hardware. This has created a network of companies across various industries whose products and services are deeply tied to NVIDIA’s technologies.

NVIDIA’s strategy to form partnerships and integrate them into its network of systems and software is beneficial to both parties. Switching to other competitors would incur significant costs and disruptions for customers. NVIDIA’s industry-wide partnerships help it have a strong and integrated ecosystem. For example, partnerships with AWS, Microsoft Azure, and Google Cloud allow NVIDIA to integrate GPUs into the cloud and make their technology available to all enterprises and developers.

In the automotive space, partnerships with Tesla and Mercedes-Benz put NVIDIA’s AI and GPU into autonomous driving, making them rely on NVIDIA AI solutions. Further, partnerships with large enterprises, such as IBM and VMware, to optimize hardware and software make NVIDIA the preferred partner for advanced computing in data centers and AI applications.

NVIDIA’s dominance may lead to increased costs of manufacturing AI chips

NVIDIA’s dominance is likely to significantly impact the world’s largest contract chip maker, TSMC (Taiwan Semiconductor Manufacturing Company), and the entire semiconductor industry.

NVIDIA is TSMC’s key customer, and the latter dedicates a big part of its production capacity to NVIDIA. NVIDIA’s pricing power impacts TSMC’s margins, and if NVIDIA decides to squeeze its suppliers to maintain its margins, TSMC is likely to feel the heat on its profitability. This could lead to capacity constraints for other customers, which will delay their product launches and drive up the prices of AI chips.

An increasing demand for AI chips from NVIDIA and others will drive up the cost of raw materials and components. This cost increase may trickle down the supply chain to end consumers. NVIDIA’s dependence on TSMC makes the supply chain vulnerable to disruptions due to China’s multi-pronged pressure on Taiwan.
NVIDIA’s dominance could drive consolidation in the semiconductor industry

NVIDIA and other companies may diversify their supply chain to mitigate the risks associated with geopolitics, supply, demand, and prices. This could lead to partnering with multiple foundries and geographic diversification. Some semiconductor companies may go for vertical integration to have more control over the value chain.

NVIDIA’s dominance and financial muscle may lead to consolidation in the semiconductor industry. Companies lacking financial resources may find it challenging to compete with big tech companies and could potentially get acquired by larger AI chip manufacturing companies.

Companies in the automotive and electronics sectors that rely on semiconductors may face procurement challenges due to supply shortages. This may lead to prioritizing high-margin products and potentially disrupting the availability of lower-margin products.

EOS Perspective

Only a limited number of global players operate in the AI chip manufacturing space, with NVIDIA holding the majority share. Startups and big tech companies are building strategies to carve out their market share.

NVIDIA will likely hold on to its market leadership with a slight dip in market share to core competitors, such as Intel and AMD, in the next few years. However, with its investments in AI R&R and its initiatives to diversify into different segments, NVIDIA might have a chance to recapture lost market share and grab new growth opportunities in the long term.

As the competition in the AI chip market intensifies, we can expect the launch of more affordable AI chips from NVIDIA competitors designed for customized AI applications. NVIDIA, on the other hand, would prioritize performance and reduce the cost of its AI chips. Since the competitors still lag in designing and developing advanced AI chips and often depend on third parties, NVIDIA is likely to capitalize and dominate the high-performance AI chip space.

With the massive and growing AI market, there is plenty of room for competitors and startups to grow even with a small market share. However, regulatory delays, sustainability issues, and unethical AI use can block strategic initiatives, increase the cost of compliance, and create uncertainty for investors and partners. Navigating these challenges will make NVIDIA more resilient and agile. The increased transparency and compliance can open up new partnership opportunities and new markets in regions where compliance is a major concern.

As AI will be the source of value for many businesses, NVIDIA will use its position to diversify by tapping into new markets to reduce its dependence on traditional markets. A potential partnership the company is discussing with OpenAI, a US-based AI research organization, will likely create a pool of new commercial opportunities for both companies to explore and monetize AI-driven solutions in the healthcare, finance, and automotive sectors.

 

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

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. PathMaker Neurosystems is 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.

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

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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.

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

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.

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

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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.

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