Following the Food and Drug Administration’s recent decision to give the green light to aducanumab, the first treatment approved for Alzheimer’s disease in nearly two decades, the agency has been loudly criticized by some for moving too quickly. In the case of another deadly neurological illness — amyotrophic lateral sclerosis, or ALS — it is moving too slowly.
Exactly one week after the aducanumab decision was made public, Amylyx, a pharmaceutical company based in Cambridge, Mass., filed a new drug submission to Health Canada for AMX0035, its promising treatment for ALS. Amylyx is also working on an expedited pathway with the European Medicines Agency. Although approval is not guaranteed by either of these agencies — the equivalents of the FDA — it would mean that Canadians and Europeans living with ALS could get this drug long before Americans.
The timeline for approval in these countries appears to be far quicker than in the U.S. Based on its interactions with the FDA to date, Amylyx has started another clinical trial of AMX0035 rather than submitting a new drug application. This suggests the FDA is requiring another trial before it will approve the drug.
FDA rules prevent ordinary Americans — in this case, disease advocates like me and people with ALS — from playing direct roles in decisions about drug approvals that are most important to us. These public actions leave me and the rest of the ALS community wondering why the pathway to approval for AMX0035 appears so much more convoluted and slower in the U.S. than in Canada and Europe.
Making approval decisions about promising treatments is never easy, especially when it comes to fatal diseases. The FDA must weigh many factors; not least among them is whether a new treatment might make a person’s health worse. The agency is right to be judicious and consider all perspectives, even in the face of pressure from patient advocacy groups. But when a new treatment has been shown to be effective and safe, the FDA has an obligation to side with people who are suffering.
In defending the FDA’s approval of aducanumab, Patrizia Cavazzoni, the director of the agency’s Center for Drug Evaluation and Research, wrote, “We ultimately decided to use the Accelerated Approval pathway — a pathway intended to provide earlier access to potentially valuable therapies for patients with serious diseases where there is an unmet need, and where there is an expectation of clinical benefit despite some residual uncertainty regarding that benefit.”
The FDA’s decision to use its regulatory flexibility is heartening. It’s exactly what the ALS community has been pushing the FDA to do for promising treatments for ALS, a fatal neurological disease for which there also is no cure and few treatments.
Amyotrophic lateral sclerosis is a rare disease; the ALS Association, which I lead, provides support to about 20,000 Americans with the disease and their families. As such, the ALS community lacks the research resources and underlying knowledge base that exists for Alzheimer’s, which affects 6 million people in the U.S. alone. There are no proven biomarkers for ALS, which serve as objective indicators of whether someone has a disease and how advanced it is, as there are for Alzheimer’s.
There are, however, promising ALS treatments in the pipeline, including AMX0035, which in clinical trials met its primary endpoint — slowed decline of function — and also extended life. The strong safety data for this drug make it clear that the risks of pursuing an approach like accelerated approval are actually low.
So here’s what puzzles me and many others in the ALS community: In the case of AMX0035 for ALS, there is evidence of clinical benefit and strong safety data but no biomarker data. In the case of Aduhelm for Alzheimer’s, there is little evidence of clinical benefit, some safety concerns, and good biomarker data. Why won’t the FDA approve AMX0035 based on clinical benefit when it approved Aduhelm based on biomarker data?
Approving a new drug for ALS — or Alzheimer’s or other diseases — can have a bigger impact than just providing people with a single new treatment. New approvals can spur innovation and investment by industry in a disease space with few available treatments available.
To be fair, the FDA advisers who resigned in protest of the Aduhelm approval no doubt believe they are putting the needs of people with Alzheimer’s first. But in cases of fatal neurological diseases without cures, when a promising drug comes along that has the potential to retain function and extend life, patients’ needs are paramount.
The FDA showed that it can — and will — use its regulatory flexibility to help people living with Alzheimer’s disease, and should be applauded for doing that. Now it needs to help people living with ALS by following its Canadian and European counterparts and offering the fastest approval path possible for people living with ALS.
Calaneet Balas is president and CEO of The ALS Association.