EAPs, Regulatory Flexibility Discussed As House Committee Meets On ALS


Developing new medicines for neurodegenerative diseases is like a quest for the holy grail. So much is still unknown about how the human brain works, and legislating approval pathways for, and access to, experimental drugs for always fatal conditions like Amyotrophic Lateral Sclerosis (ALS) and Huntington’s disease is not an easy task. 

So on Thursday, the U.S. House Energy and Commerce Subcommittee on Health held a series of panels entitled “The Path Forward: Advancing Treatments and Cures for Neurodegenerative Diseases.” Much of the discussion centered around ALS, a brutal degenerative illness that takes the lives of most of its victims within 3-5 years from the time of diagnosis. 

There were impassioned pleas for reform from house members, including Health Subcommittee Chair, Rep. Anna Eshoo (CA-18) and Rep. Frank Pallone, Jr. (NJ-06), along with Dr. Merit Cudkowicz, Director of The Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital.

The panels discussed key issues such as expanded access programs (EAPs), clinical trial diversity, conditional approval pathways, and patient experience data. Overall, an optimistic note was struck. 

“There are thousands of scientists in the field, new brilliant insights into the underlying disease biology, more than 160 companies with ALS drugs in pipeline, several treatments with positive phase 2 and 3 trial results in people already and the first platform trial approach to speed drug development is enrolling faster than any previous trial. We are at a major therapeutic turning point for ALS,” Cudkowicz said in her written statement. 

Patrizia Cavazzoni, M.D., Director of the FDA’s Center for Drug Evaluation and Research (CDER), was more reticent when responding to a question about the possibility of accelerated approval pathways for neurodegenerative diseases such as the EU’s conditional marketing authorization (CMA). 

“A limiting factor in applying all of the tools that we have, such as accelerated approval for instance, is really the lack of understanding of the biology of the diseases,” Cavazzoni said. “We're very eager to work with sponsors to identify some of the biomarkers and the markers of disease that would allow us to utilize our expedited pathway, including accelerated approval, in neurodegenerative diseases to accelerate their development.”

Cudkowicz provided the example of Amylyx’s ALS drug, AMX0035 as one such candidate for an accelerated approval pathway.

“Our partnership with the two founders of Amylyx culminated in a two-drug combination that BOTH slows disease progression AND prolongs survival,” she wrote. “AMX0035 is under review in Canada for full approval. It will be submitted to EMA for provisional approval. We do not currently have that regulatory option for ALS in the United States. A drug developed and tested in the United States will likely be approved elsewhere before approval in the United States.” 

Cudkowicz implored House committee members to approve two pieces of legislation. One, the Accelerating Access to Critical Therapies (ACT) for ALS Act, would increase access to EAPs for ALS patients, while the other, the Promising Pathway Act, would allow for the conditional approval of promising treatments in Phase II and III.

“EAPS can be designed to also learn about ALS. For example, in one of our EAPs, we learned about how to best dose the medication, using biomarkers. In another, we found that breathing function improved in several of the participants. Expanded access absolutely does not interfere with clinical trials and drug development. It can help it,” Cudkowicz said. 

Dr. Cartier Esham, Chief Scientific Officer and EVP of Emerging Companies at the Biotechnology Innovation Organization (BIO) presented numbers that displayed an inequity in drug development and FDA approvals across disease spaces.

“In 2021, we counted 653 clinical development programs for medicines to treat neurological diseases, 43% of which are for neurodegenerative diseases. By comparison, there are 2798 oncology clinical development programs. There have only been a total of 39 FDA approvals for neurological treatments in the past decade compared to 123 for oncology,” she said.

ALS advocate, Michelle Lorenz, told BioSpace about the “glimmer of hope” that was sparked in the ALS community during the clinical trials of BrainStorm Cell Therapeutics’s NurOwn. In February, the FDA told BrainStorm that evidence from the phase III trial of NurOwn did not meet the threshold required for a Biologics License Application (BLA). 

“Their hope has been resurrected now with so many in the NurOwn EAP regaining function again - for a second time! But that hope needed to be validated. It wasn't enough that they believed,” Lorenz said. “With their questions, Congress told the FDA they believe it now too. Yesterday's Congressional hearing became the first time we've dared to believe that hope may become a reality!” 


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