Like many brain diseases, amyotrophic lateral sclerosis (ALS, commonly known as "gradual freezing syndrome") is still a difficult target for drug developers. Promising therapies have failed again and again, putting increasing pressure on the next possible therapy. Currently, only two drugs are used to combat this disease, and both have their limitations.

Among the new drugs under development, the most concerned one comes from Amylyx Pharmaceuticals in Cambridge, Massachusetts. Last year, the results of a small study showed that compared with patients who received a placebo, patients treated with Amylyx's drug (AMX0035) showed improvements in basic functions such as speaking, walking, and writing. The study also found that after receiving AMX0035 treatment, patients' functional decline was slower and life span was longer.

With these results, Amylyx concluded that it has sufficient evidence to seek approval. In March of this year, the company stated that it would submit a marketing application to Health Canada in the first half of this year. On Wednesday, the company announced that it plans to submit a marketing application to EU regulators before the end of 2021.

But in the United States, the regulatory time may be much longer, because Amylyx also just revealed that the US FDA hopes to see data from an additional placebo-controlled study before the company submits the AMX0035 marketing application. In order to meet this requirement, Amylyx intends to carry out a late-stage clinical trial in Europe and the United States, and it is expected to start enrolling patients from July to September.

Amylyx executives stated that they will cooperate with the FDA to meet these data requirements as soon as possible. Nonetheless, Wednesday’s statement raised more questions about this unusual regulatory case.

Under normal circumstances, the FDA is the first stop for pharmaceutical companies to seek regulatory approval in the pharmaceutical market. Especially when the company is headquartered in the United States or operates some clinical projects in the United States. However, Amylyx first submitted AMX0035 listing applications in Canada and Europe, and then applied in the United States.

Josh Cohen, co-founder and co-CEO of Amylyx, said in an interview with BioPharma Dive in March: "What I want to say is that Health Canada has been working with us very quickly. Frankly, I think the FDA is also here now. A little bit, but it took them a while to recover."

For patient groups such as the American ALS Association (The ALS Association), the US shutdown reflects a bigger problem for the FDA. In a statement, the association condemned the FDA, saying that the agency did not try to launch new ALS therapies as soon as its peers did.

Calaneet Balas, Chairman and CEO of the ALS Association, said in a statement on Wednesday: "Americans with ALS deserve potentially beneficial treatments that Canadians and Europeans will soon get. We have asked the FDA to approve AMX0035 as soon as possible. But to So far, these calls have been ignored."

It is worth noting that the FDA's position on AMX0035 was raised shortly after another experimental drug for the treatment of ALS caused controversy. At the end of last year, a New York biotechnology company named Brainstorm Cell Therapeutics disclosed that its stem cell-based ALS therapy did not meet the main goal of a later trial. Despite the failure, Brainstorm CEO Chaim Lebovitz expressed confidence in continuing to advance this stem cell therapy.

However, by February, the prospects for approval seemed bleak. Brainstorm said that it has received a response from the FDA, and the agency believes that there is insufficient evidence to support the listing application.

This statement was also strongly condemned by patient groups and advocates, who blamed the FDA for not recognizing the urgent need for new treatments for ALS. Brainstorm can still submit an application without additional data, although it is unlikely to be approved after the FDA's feedback.

Following these criticisms, the FDA took the unusual step of explaining its position on Brainstorm’s stem cell therapy in a press release. The agency said: “From the data that has been communicated to the ALS community, people very much hope that this product can provide at least a moderate breakthrough in the management of ALS, if not a more substantial breakthrough. However, the results of the later research. Shows that the data clearly does not support the clinical benefits of this therapy."

Since then, the ALS Association has made an unusual voice of its own. Earlier this month, after Calaneet Balas was hit by a "dangerous and vulgar social media attack," the board of directors of the association clearly stated its support for Balas.

Reference source: FDA faces backlash after seeking more data on an experimental ALS therapy