Amylyx Seeks Approval in Canada of Lead Candidate AMX0035

Amylyx Pharmaceuticals is seeking approval, in Canada, of its lead candidate AMX0035 for the treatment of amyotrophic lateral sclerosis (ALS).

This regulatory submission “represents a significant milestone in our efforts to develop a new treatment option for people living with ALS who have no time to wait,” Joshua Cohen, co-founder, co-CEO, and chairman of Amylyx, said in a press release.

Chris Aiello, Amylyx’s head of Canada and general manager, said the company “is committed to bringing AMX0035 through the regulatory approval process as quickly as possible” in the country, as its staff continues to “work closely with Health Canada.”

The company also is working to make the therapy available in Canada before a regulatory decision, possibly through a special access program run in collaboration with the Canadian ALS Research Network. These plans are expected to be finalized by the close of June.

Tammy Moore, the CEO of ALS Society of Canada, emphasized that “there is a critical and urgent need for people living with ALS to have equitable, timely and affordable access to proven therapies.”

“Amylyx’ decision to pursue regulatory approval of AMX0035 is an important step forward for this community who continues to face a devastating disease,” Moore said.

A similar regulatory application is expected to be filed with the European Medicines Agency (EMA) by the end of this year. The EMA is responsible for regulating medications for the European Union countries.

Meanwhile, the U.S. Food and Drug Administration (FDA) has requested data from an additional placebo-controlled clinical trial before considering AMX0035 for approval.

To that end, Amylyx plans to launch a global Phase 3 trial in the coming months to test AMX0035 against a placebo in up to 600 ALS patients. Results from the PHOENIX trial, to be conducted at 55 sites across the U.S. and Europe, are expected to support a regulatory application with the U.S. agency.

The ALS community has urged the FDA for the earliest possible approval of AMX0035 through several means, including a November petition signed by more than 50,000 people, and a May virtual meeting with the U.S. agency that was hosted by The ALS Association.

At that meeting, eight people living with ALS shared their views on the importance of new therapies and incremental gains, and the risks they are willing to take.

Amylyx continues to discuss the best path for AMX0035’s approval with health authorities around the world, the company said in the release.

AMX0035 received orphan drug designation in both the U.S. and Europe, which helps to speed its development by providing regulatory support and financial benefits, as well as a marketing exclusivity period — for seven years in the U.S. and 10 in Europe — upon regulatory approval.

The therapy is a fixed-dose combination of two orally available, neuroprotective molecules. Both tauroursodeoxycholic acid and sodium phenylbutyrate are already used in the clinic and have proven to be safe and well-tolerated.

Together, they 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.

The new regulatory submission in Canada was based on positive data from the CENTAUR Phase 2/3 trial (NCT03127514), which evaluated AMX0035’s safety and effectiveness in 137 adults who had recently been diagnosed with sporadic or familial ALS.

All had evidence of rapidly progressing disease — a stringent enrollment criteria meant to provide the most powerful results possible — and were randomly assigned to receive either AMX0035 or a placebo, twice daily for 24 weeks (almost six months).

Most eligible patients who completed the trial (92%) chose to enter its open-label extension study (NCT03488524), in which all are receiving the therapy for up to 30 months (about two and a half years).

CENTAUR’s top-line results showed that AMX0035 significantly slowed patients’ functional decline — as assessed with the ALS Functional Rating Scale-Revised — independently of other medication use or duration, meeting the trial’s main efficacy goal.

In addition, nearly three years of follow-up spanning both CENTAUR and its extension study showed that patients initially assigned to AMX0035 had a 44% lower risk of death, tracheostomy or permanent assisted ventilation, or first hospitalization, compared with those randomized to a placebo. Tracheostomy is a surgical procedure to create an opening in the windpipe for mechanical ventilation.

These patients also lived significantly longer — 25 months vs. 18.4 months, representing a 44% lower risk of death — than those randomly assigned to receive a placebo.

The therapy was generally safe and well-tolerated, and associated with early, generally mild, gastrointestinal side effects.

“We’d like to thank the people who participated in CENTAUR, trial investigators, the ALS community and our partners and team, who have worked tirelessly to help us achieve this milestone,” said Justin Klee, Amylyx’ co-founder and co-CEO.