ALS Drug Developer Cashes In on FDA’s Precedence in Alzheimer’s Disease
(Thursday, September 16, 2021)
FDA reversed its decision regarding the inadequacy of a small Phase 2 trial for the approval of a new drug for ALS under pressure from patient groups setting up yet another precedence for other similar developers of drugs for rare diseases with questionable data. Accepting this market approval application will set FDA to being forced to approve this drug with data that FDA does not believe is adequate. For patients with ALS, this may seem like better news, but is it? Earlier this year, in February, FDA had told Amylyx, the developers of AMX0035 for ALS, that the data from its Phase 2 trial in 137 patients does not support the proposed clinical benefit of this therapy and that it needed to be repeated in a larger and longer clinical trial. Ironically, this was the same conclusion that the company had also reached as it wrote in the publication based on the Phase 2 trial. However, after FDA approved Aduhelm for Alzheimer’s disease in June, the ALS patients support groups mounted enormous pressure on FDA to do the same for AMX0035. By relenting, FDA just may have opened a flood gate for similar pressure from all similar situations. It is not hard to relate with the ALS patient groups who have loved ones with this terrible disease and who would want to grasp any thread to give hope to the patients and their families. And for the company, there are obvious business reasons to push for faster approval. The Phase 2 trial involved practically every Who’s Who in the medical community in the US working in ALS research showing that the drug has significant support from the ALS research and medical community. But one cannot deny that a trial which showed modest benefits in 89 patients treated with the drug for 24 weeks, is likely insufficient to be allowed to be used in the 30,000 patients who are affected by it and would need life-long treatment with the new drug. The publication for the trial acknowledged several limitations of the surrogate endpoint used as the primary endpoint in the study, and the study population (70% males, 94% white, etc.). The company did not present any new data to convince FDA after being told about FDA’s comments in February, so the only reason FDA reversed its decision seems to be due to the pressure from patients. While patients are right-fully emotional and biased to get these treatments available, FDA’s job is to be unbiased, balanced, and fair, to always protect the patient’s interest, even it means rejecting drugs that have not yet established reasonable evidence of benefits to the patients that they are intended for. This reversal is far from it. This is becoming an age of activist patients who believe that something is better than nothing at any cost, and smart companies that use support from such patient groups to pressure FDA for favorable decisions when their clinical data won’t be enough to move the regulatory needle. This regulatory business strategy can be traced back to the female libido drug, Addyi, but was really exploited by Sarepta for its treatment for Duchenne’s Muscular Dystrophy (DMD), and then used by Biogen for Aduhelm, and now by Amylyx for its ALS drug. While this strategy has generated enormous wealth for the developers, patients may not have benefited much more than getting hope from questionable treatments. And it certainly dents the FDA’s claim of being a “science-based” regulatory agency.
Dr. Mukesh Kumar
Founder & CEO, FDAMap
Linkedin: Mukesh Kumar, PhD, RAC