Why digital biomarkers will power tomorrow’s Alzheimer’s therapies

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Rivka Kreitman, CIO of NeuraLight explores the landscape of therapies for Alzheimer’s and explains why digital biomarkers are key to combatting the disease.

Neurodegenerative diseases – the collection of progressive conditions characterised by neuron cell damage and death and subsequent loss of motor function – represent a significant burden for patients, their caregivers, and the healthcare system. Diseases such as Alzheimer’s, amyotrophic lateral sclerosis (ALS), and Parkinson’s remain without disease-modifying treatments, and the development of drugs to slow the progress of these debilitating conditions has been a challenging task.

However, recent advances, such as the FDA approval of RELYVRIO to slow the progression of ALS and the accelerated FDA approval of Eisai and partner Biogen’s intravenous lecanemab, demonstrate significant headway in the development of therapies for neurodegenerative diseases. As the industry rides this momentum, it will be essential to invest in the development and use of reliable and objective methods for measuring, diagnosing, and monitoring these conditions to ensure the continued success and effectiveness of therapies for neurodegenerative diseases.

But there are still challenges facing the development of therapies for neurodegenerative diseases, and a few emerging technologies can be used to measure the efficacy of such advances.

Breaking the barrier

Earlier this year, two drugs demonstrated slowed disease progression in large-scale clinical trials for ALS and Alzheimer’s. In September, Amylyx Pharmaceuticals received FDA approval for its ALS drug, AMX0035 (rebranded RELYVRIO), which demonstrated slowed disease progression and functional decline as well as extended survival – the first ALS drug to do so in a randomised clinical trial. A press release about the historical achievement claimed that, “A key factor for Relyvrio is its function and survival benefit, which is historically a difficult endpoint to accomplish, and one no other treatment can claim.”

Another drug that is reported to have slowed progression of a neurodegenerative disease: an experimental Alzheimer’s drug produced by Japanese pharma company Eisai and its partner Biogen – which recently underwent a successful Phase III clinical trial – won accelerated FDA approval this year.

In an interview in Tokyo, Naito claimed: “The data is indisputable. The drug met primary and secondary endpoints perfectly and has a manageable safety profile.” He added that US approval will pave the way to “broad coverage under Medicare insurance for elderly Americans,” a prospect that brings hope to the over six million Americans suffering from Alzheimer’s disease and their caretakers.

Exciting as these results may appear, however, significant challenges remain in establishing the efficacy and safety of these drugs and making subsequent advances for neurology routine. Speaking of ALS, Amylyx’s Co-founder and co-CEO Josh Cohen said there are still a number of unaddressed, long- standing problems, including “diagnoses that take too long, woefully underfunded clinics, and challenges barring access for patients.” And although Amylyx is dedicated to addressing these issues for ALS specifically, these challenges are shared across the neurodegenerative disease drug development landscape.

The challenges facing neurodegenerative disease drug development

One of the major hurdles in developing effective drugs for neurodegenerative diseases is the lack of reliable and objective methods for evaluating, diagnosing, and monitoring these conditions. Compared with cancer, cardiovascular disease, and even infections, which have well-described biomarkers for detection and diagnosis, biomarkers for neurodegenerative diseases lag far behind.

Biomarkers are necessary for developing effective drugs for neurodegenerative diseases. They are powerful tools for patient stratification, which is the cornerstone of precision medicine. Accurate biomarkers are necessary for identifying patient subpopulations and enrolling them in clinical trials for drugs that are specifically designed for their disease. To develop more drugs that can slow disease progression, it is essential to improve our understanding of the underlying mechanisms of neurodegenerative diseases and identify accurate biomarkers for diagnosis and tracking disease progression.

Another major roadblock is the lack of understanding of the mechanisms of disease development and progression. Key underlying molecular defects that contribute to disease progression serve as precise targets for novel drugs. However, knowledge gaps in this area for several neurodegenerative conditions make it difficult to know where to begin to develop drugs. Without a clear understanding of the underlying mechanisms of these diseases, it is difficult to identify potential targets for drug development.

Additionally, the complexity and heterogeneity of neurodegenerative diseases make it difficult to develop effective treatments. These conditions often involve multiple factors, such as genetics, environmental exposures, and lifestyle factors, that can interact in complex ways to cause or contribute to disease. As a result, it is difficult to identify a single target for drug development that would be effective across all patients with a given neurodegenerative disease. The complexity of these conditions poses a significant barrier to the development of effective drugs.

How technology can help

Advances in artificial intelligence (AI) and other technologies have touched multiple aspects of our lives, and medicine is no exception. There is huge potential for modern technology to aid in the identification of biomarkers for neurodegenerative diseases to not only identify novel drug targets but also to design and execute clinical trials that accurately assess the efficacy of new drugs. For example, these technologies can facilitate objective, reliable, and sensitive measurements, power easy integration into existing research facilities, ensure that new therapies reach clear and quantifiable endpoints, improve the scientific merit of biomarker discovery studies, and inform appropriate patient stratification.

There are several companies leveraging technology to address many of these opportunity areas. Between using AI to extrapolate how tiny eye movements, exercises completed on a smartphone, and typing on a touch screen indicate neurological disease, these companies are identifying biomarkers for a set of conditions that have long evaded accurate biomarker detection. Leveraging technologies that patients already use in their everyday lives, these emerging solutions are lowering the participation barrier for charting the progression of neurological disease.

While Amylyx, Eisai, and Biogen have shown us significant promise for the creation of disease-modifying drugs, the true unleashing of drug development for neurodegenerative disease will come from objective biomarkers that can evaluate patients and track the progression of disease, reduce inter-rater variability, and improve the reliability of research findings. With the proliferation of novel biomarkers for neurodegenerative diseases, we can expect to see a new wave of promising advancements.

Rivka KreitmanAbout the author:

Rivka Riven Kreitman is the Chief Innovation Officer of NeuraLight. Before joining NeuraLight, Kreitman spent 26-plus years at Teva Pharmaceuticals in roles including Head of Global IR&D and Head of Global Specialty Regulatory Affairs. Kreitman earned her PhD at the Weizmann Institute of Science and completed postdoctoral work at Princeton.

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