ALS Association Supports FDA Reconsidering AMX0035 Decision

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by Marta Figueiredo PhD |

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The ALS Association is applauding the recent change of heart by the U.S. Food and Drug Administration (FDA) to consider AMX0035’s approval for amyotrophic lateral sclerosis (ALS) without requiring results from an additional clinical trial.

Earlier this year, the agency had requested data from a placebo-controlled Phase 3 trial, PHOENIX (NCT05021536), before considering Amylyx Pharmaceuticals’ investigational oral therapy for approval.

Following Amylyx’ upcoming, FDA-consented regulatory submission for AMX0035, the association urges that the therapy be approved as soon as possible for all people living with ALS.

“We are excited that people with ALS may soon have another treatment option that will help make ALS livable,” Calaneet Balas, the ALS Association’s president and CEO, said in a press release.

“We are further encouraged that the FDA appears to have finally heard the loud and clear message from the ALS community that people with ALS are willing to accept greater risk to try potential treatments,” Balas added.

In November, the ALS Association and I AM ALS filed a petition, signed by more than 50,000 people, asking that AMX0035 be approved based on positive results from the completed CENTAUR Phase 2/3 trial (NCT03127514).

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Since then, the ALS Association also held several meetings with FDA officials, culminating in a May call-to-action meeting, in which eight ALS patients shared their perspectives with 17 officials on the importance of new therapies and incremental gains, and the risks they are willing to take.

“The ALS community has been united in this effort and we expect the FDA to act quickly,” said Larry Falivena, who is living with ALS and is a member of the association’s board of trustees.

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

Besides regulatory, medical, and research counsel to help accelerate AMX0035’s development, the ALS Association also supported a previous pilot trial and the CENTAUR study through donations received during the ALS Ice Bucket Challenge. More than $2 million was given in the form of grants.

Balas said the Ice Bucket Challenge “led to new ALS genes being discovered, greater access to care services for people with ALS and their families, and in AMX0035, a very promising new treatment that could make a difference for thousands of people with ALS.”

“We continue to see the impact of the millions of people around the world who took the Challenge in the summer of 2014 and we are forever grateful to the people with ALS and families who started it. They truly changed the trajectory of ALS forever,” Balas added.

In a related blog post, Neil Thakur, PhD, the ALS Association’s chief mission officer, stated “these are positive steps toward making ALS livable and eventually curing it.

“Until we have a full cure for everyone with ALS and everyone who might get it in the future, we have to do everything in our power to make ALS livable,” meaning longer, better lives, with reduced disease-associated physical, emotional, and financial burden, Thakur added.

He also noted that therapies providing incremental benefits, such as AMX0035, are “very important, as these drugs can work in concert with other existing treatments and technologies.”

AMX0035 combines two small molecules in clinical use, tauroursodeoxycholic acid and sodium phenylbutyrate, that are known to be safe, well-tolerated, and to protect neurons from cellular stress-induced damage.

In the CENTAUR study, six months of treatment with AMX0035, given twice daily, were found to be generally safe and to significantly slow ALS patients’ functional decline, compared with a placebo.

The trial involved 137 adults recently diagnosed with sporadic or familial ALS and with rapidly progressing disease. Most chose to enter its open-label extension study (NCT03488524), in which all are receiving the therapy for up to two-and-a-half years.

Long-term data from both studies showed that patients receiving AMX0035 in CENTAUR had a 44% lower risk of death relative to those initially assigned a placebo.

The global PHOENIX trial, expected to start soon, is designed to confirm these positive findings in up to 600 ALS patients, who will be recruited at 55 sites across the U.S. and Europe and assigned randomly to receive either AMX0035 or a placebo for about 11 months.

Also, details of a potential Amylyx-led Expanded Access Program in the U.S., which would provide ALS patients early access to AMX0035, are expected later this year. If implemented, the program would run in parallel with the FDA’s application review and the PHOENIX trial.

Notably, similar regulatory applications of AMX0035, supported by CENTAUR findings alone, are currently being reviewed by Health Canada and poised for filing with the European Medicines Agency by the end of the year. Amylyx also is working with health authorities elsewhere to determine the best path for approval in their respective countries.