ALS Association Wants More Commitment From the FDA

In a response letter to The ALS Association, the U.S. Food and Drug Administration (FDA) has recognized the unmet therapeutic need of people with amyotrophic lateral sclerosis (ALS) and reaffirmed its commitment to the 2019 ALS clinical trial guidance.

However, the agency did not provide any details about how it has implemented that guidance to date — a specific request made by the association shortly after hosting a virtual meeting with the FDA in May.

The meeting was meant to reinforce the importance of incremental gains to ALS patients and the risks they are willing to take with new therapies. During the meeting, eight people living with ALS shared these perspectives directly with Patrizia Cavazzoni, MD, director of the FDA’s Center for Drug Evaluation and Research (CDER) and other FDA officials.

In the response letter, Cavazzoni wrote: “We recognize the continued unmet need for treatments for patients living with ALS and are committed to engaging with companies and the patient community to facilitate the development of treatments for this disease.

“We can also assure you that we are exercising the regulatory flexibility described in FDA’s 2019 [ALS] guidance … and we continue to commit to doing so,” Cavazzoni stated, noting that the amount of information the agency can provide about specific development programs is limited.

While FDA’s recommitment to the guidance is encouraging, “the ALS community deserves to know exactly what the FDA is doing to help expedite approval of promising treatments,” The ALS Association stated in a blog post.

The association thinks the FDA does not appear to be using the guidance and associated regulatory flexibility to approve promising ALS treatments, such as Amylyx Pharmaceuticals’ experimental therapy AMX0035, as soon as possible.

The CENTAUR Phase 2/3 clinical trial (NCT03127514), which evaluated the safety and effectiveness of six months of treatment with AMX0035 in 137 adults recently diagnosed with rapidly progressing ALS, met both its main efficacy and safety goals.

AMX0035 was generally well-tolerated and significantly slowed patients’ functional decline independently of other medication use or duration, compared with a placebo. Longer-term treatment also was found to reduce the risk of death, hospitalization, and permanent ventilation.

While Canadian and European regulatory agencies are working with Amylyx to move the treatment toward approval as fast as possible based on available trial results, the FDA required an additional placebo-controlled trial, which is likely to begin in upcoming months, according to Amylyx.

While approval in Canada and the European Union is not guaranteed, The ALS Association estimates AMX0035 may be available to ALS patients in Canada by the end of the year possibly via a special access program. Amylyx also filed a regulatory application to Health Canada early this month.

In turn, “it could be several years before Americans with ALS are able to access AMX0035, if at all,” the association stated.

The ALS Association also emphasized that the U.S. agency has recently used its regulatory flexibility to conditionally approve Aduhelm (aducanumab) for the treatment of Alzheimer’s disease after a tumultuous clinical path.

“We are left to wonder the FDA is not using similar flexibility for a promising ALS treatment with strong safety data that provides clinically meaningful benefits. People with ALS and their loved ones cannot wait,” the association stated.

The association plans to keep putting public pressure on the FDA, as it has done in a recent comment in an Endpoints article and a guest opinion in Stat News and through a November petition for AMX0035’s earliest approval signed by more than 50,000 people.

It also will continue to work with the U.S. agency and pharmaceutical companies behind the scenes to speed therapy development for ALS, and to seek greater public accountability for the FDA.

Moreover, the association is supporting ACT for ALS, which will create a new framework for delivering experimental therapies to ALS patients, and the Promising Pathways Act, which will provide a conditional approval pathway for investigative medications that show good safety and evidence of efficacy in early trials.