FDA Grants Priority Review to ALS Therapy AMX0035

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by Steve Bryson, PhD |

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The U.S. Food and Drug Administration (FDA) has accepted for review Amylyx Pharmaceuticals‘ application seeking approval of AMX0035 for the treatment of amyotrophic lateral sclerosis (ALS).

The new drug application (NDA) also was granted priority review by the regulatory agency, which reduces review time from the standard 10 months to six months. A decision by the FDA is expected by June 29. Meanwhile, the agency is planning to hold an advisory committee meeting to discuss the application.

“We are excited about this milestone and are preparing our team to be able to launch commercially if the FDA review results in an approval,” Justin Klee, co-CEO, director, and co-founder of Amylyx, said in a press release.

The company has a similar application under review in Canada, and intends to seek approval for the therapy in Europe in the coming months.

“Our team is committed to bringing a potential new treatment, if approved, to people living with ALS as efficiently as possible, as each moment counts,” added Joshua Cohen, Amylyx’s co-CEO, co-founder and chairman.

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AMX0035 is a fixed-dose combination therapy containing two small molecules: sodium phenylbutyrate and tauroursodeoxycholic acid. Individually, these medicines have been used in the clinic and have demonstrated a good safety profile.

The treatment is designed to prevent nerve cell death by blocking stress signals in energy-producing mitochondria and the endoplasmic reticulum, a component within cells involved in protein production, modification, and transport.

The application was based on data from the six-month CENTAUR Phase 2/3 clinical trial (NCT03127514), which investigated AMX0035 versus a placebo in 137 adults recently diagnosed with ALS and whose disease was progressing rapidly.

Almost all participants (92%) who completed CENTAUR then chose to enter its open-label extension (OLE) study (NCT03488524), which included up to 30 months of AMX0035 treatment (about two-and-a-half years).

Top-line results demonstrated the therapy significantly slowed functional decline and prolonged survival compared with a placebo. Findings from the CENTAUR and OLE periods also showed that participants initially assigned AMX0035 in CENTAUR lived significantly longer than those initially on placebo — a median of 25 months vs. 18.5 months — representing a 44% lower risk of death.

“Those living with ALS are in urgent need of new therapies,” said Sabrina Paganoni, MD, PhD, principal investigator of the CENTAUR trial. “If approved, AMX0035 may provide people with ALS more shared memories and quality time with their loved ones.”

Initially, the FDA said it needed additional data from the larger Phase 3 PHOENIX trial (NCT05021536) before considering AMX0035 for approval. However, after recent discussions with the agency, Amylyx submitted an application based on CENTAUR data alone.

Dosing has begun in the PHOENIX trial, which is expected to include up to 600 participants whose symptoms started in the past two years — a less-stringent criteria than required for the CENTAUR trial.

Participants will be assigned randomly to take a placebo or AMX0035 for 48 weeks (about 11 months). The trial will assess changes in a joint assessment of functional decline, measured with the ALS Functional Rating Scale-Revised (ALSFRS-R), and survival. Secondary outcomes include changes in lung function, the need for ventilation, and quality of life.

Enrollment is ongoing at 65 sites in the U.S. and Europe, as part of collaborations with the Northeast ALS Consortium (NEALS) and the Treatment Research Initiative to Cure ALS (TRICALS), respectively.

“There is a lot of progress in ALS research; and now with AMX0035’s NDA acceptance, we believe we are one step closer to a potential new treatment option,” said Merit Cudkowicz, MD, co-principal investigator of the CENTAUR trial and co-founder of NEALS.

“We look forward to seeing AMX0035 potentially progress through the regulatory review process as we continue to investigate its therapeutic potential in the global Phase 3 PHOENIX clinical trial as part of the collaboration with the Northeast ALS (NEALS) Consortium and the Treatment Research Initiative to Cure ALS (TRICALS) in Europe,” Cudkowicz said.

Amylyx said it also is preparing to submit an expanded access program (EAP) in the U.S. in the coming months, which would provide access to AMX0035 in ALS patients who are ineligible for the PHOENIX trial. If approved, the EAP will run alongside the PHOENIX trial and the NDA review.

“The acceptance of our NDA for review by the FDA brings us one step closer to bringing a potential new treatment to people living with ALS,” said Tammy Sarnelli, Amylyx’s global head of regulatory affairs. “We thank everyone who participated in the CENTAUR trial, including the trial investigators, the ALS community, our partners and our team.”