The FDA Made History in ALS: What’s Next?

By Diego Cadavid, M.D, FAAN, FANA, Chief Medical Officer

I went into medicine to help people living with devastating neurological diseases, not the least of which includes amyotrophic lateral sclerosis (ALS). As a practicing neurologist and drug developer for 20+ years, I’m constantly working to better understand the disease and searching for different approaches to help improve outcomes for patients.

Thankfully a lot is happening now in the ALS field that gives us reason for optimism.  Although the unmet need remains quite high, in the last few years and as recently as in the last few days, new ALS therapies have been approved in the US. 

Why? Emerging science, including a better understanding of the cause of the disease and new drug development tools, has been met with regulatory flexibility to create a new path forward for drug development and approval in ALS. 

For the first time, the U.S. Food and Drug Administration (FDA) approved (under the accelerated approval pathway) a new treatment for a rare familial form of ALS. This approval was based on a strong reduction in levels of a blood biomarker of neuronal degeneration called neurofilament light chain. This approval is very important not only for the families affected by this devastating familial form of ALS that now have access to a treatment, but also because it shows that the FDA is willing to approve an ALS drug based on the ability of a blood biomarker that is likely to predict that drug’s efficacy.

Biomarkers like neurofilament light chain have a great potential to improve the efficiency and success of drug development, especially in neurological disorders, ​​and I believe they will be transformational for the field. These tools can precisely, and with great sensitivity, measure changes in biological markers of disease activity and severity. Great progress is also happening with biomarkers of clinical function that can measure changes in key clinical impairments of the disease, such as mobility, breathing, speech and muscle strength in the case of ALS. I see parallels in the evolution of these ALS biomarkers to the advances I witnessed while working on MS drugs for patients at Biogen. We owe the development of so many drugs for the treatment of relapsing forms of multiple sclerosis in the last 3 decades to a large extent to imaging biomarkers of brain inflammation. We are heading towards a future where biomarkers enable us to learn more and faster than ever about neurological disorders like ALS and their candidate treatments. This should translate into more rapidly discovering and developing better drugs for patients who can’t wait.

I applaud FDA’s flexibility in the approval of new therapies for rare neurological diseases with high unmet need and their embrace of fluid and clinical digital biomarkers as valuable tools that can provide evidence of efficacy.  We are in the middle of a revolution in neurology drug development where biomarkers will increasingly play a critical role in evaluating novel drug candidates and supporting drug approvals.

There is more we can and must do, and it starts with developing disease modifying drugs that treat all forms of ALS. At Verge, we are preparing to launch the first in-patient clinical trial of our small molecule VRG50635 in people with sporadic and familial ALS. For this we are planning a state of the art proof of concept clinical trial rich in both fluid biomarkers, such as neurofilament light chain and neuronal derived exosome proteins and gene transcripts, and digital clinical biomarkers that measure core clinical impairments. I believe this combination of fluid and clinical digital biomarkers in the context of a clinical pharmacology study to investigate safety and efficacy of increasing doses of VRG50635 has great potential to get to proof of concept faster and with greater confidence, and in turn accelerate the clinical development of therapies for patients to whom time means everything.