50K-signature Petition Calling for Swift Approval of AMX0035 Given FDA, Amylyx

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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The ALS Association and I AM ALS have filed a petition with the U.S. Food and Drug Administration (FDA), calling on the regulatory agency and Amylyx Pharmaceuticals to make AMX0035 available to people with amyotrophic lateral sclerosis (ALS) as quickly as possible.

Signed by more than 50,000 patients, their caregivers and family, the petition asks the FDA to approve the medication based on highly promising Phase 2 safety and efficacy data, without waiting for confirmation in a larger Phase 3 clinical trial.

“The ALS community has united to ask the FDA and Amylyx to make AMX0035 available as soon as possible,” Larry Falivena, an ALS patient and member of the association’s national board of trustees, said in a press release.

“Given the promise that AMX0035 shows in slowing progression and its safety record, the community should not have to wait several more years for another clinical trial. Thousands of us who could have been helped will have passed from this devastating disease,” Falivena added.

AMX0035 is a combination of two small molecules, tauroursodeoxycholic acid and sodium phenylbutyrate, already in clinical use and known to be safe and well tolerated. The combo works to prevent nerve cell death by blocking stress signals within mitochondria — the cells’ powerhouses — and the endoplasmic reticulum, a cellular organelle involved in protein production, modification, and transport.

It showed promising results in ALS patients with rapidly progressing disease in the 24-week Phase 2 trial known as CENTAUR (NCT03127514), and its open-label extension study CENTAUR-OLE (NCT03488524).

In CENTAUR, 137 recently diagnosed adults with rapid progression were given oral AMX0035 or a placebo twice daily. Treated patients experienced significant reductions in the rate of functional decline, in measures that included speech, swallowing, walking, dressing, and hygiene. In the OLE study, those on continuous treatment lived a median of 6.5 months longer than did patients who switched from placebo to treatment — reflecting a 44% lower risk of death.

AMX0035’s use was considered safe, and its efficacy was found to be independent of the use and duration of other treatments. Patients on this medication also showed a trend toward slower decline in muscle strength and lung function, and fewer hospitalizations.

While a larger Phase 3 confirmatory trial would normally be required for FDA approval, the petition is asking that Amylyx submit these Phase 2 data to the regulatory agency, and that the FDA approve the medication.

The petition notes that ALS patients are willing to accept more risk until effective treatments are found, due to the deadly nature of their disease.  It asks for a swift approval that allows marketing, with more rigorous studies conducted after the treatment is available to those in need.

“I  agree with and understand the FDA’s  interest in protecting people from harmful or misleading drugs,” said Tommy May, a member of the ALS Association’s national board of trustees, diagnosed with ALS in 2005.

“ALS should be treated differently, however, and the FDA has acknowledged that. People living with ALS are willing to tolerate much greater risk and have expressed this to the FDA for years.  I can attest to that,” May said.

“To date there has not been one ALS survivor and it’s time we change that,” added Sandy Morris, patient advisory council co-chair for I AM ALS. “The results from the AMX0035 trial have given our community great hope and we look to you as the leaders to move forward with urgency. ALS waits for no one and we must be equally as relentless.”

The association release also noted that the trial’s “level of statistical significance is not strong enough to make a decision to skip phase 3 obvious or uncontroversial. Skipping a phase 3 study remains a hard decision for the FDA to make,” and a further reason for the petition’s importance.

This petition, it added, is also supported by the FDA’s own guidance for ALS clinical trials, in which the agency “has long stressed the appropriateness of exercising regulatory flexibility” when dealing with “drugs for serious diseases with unmet medical needs.”