The company will also explore options for early access to the therapy for patients in the country. One possibly route is via a special access program run in collaboration with the Canadian ALS Research Network, the company announced in a press release.
Both the approval request, in the form of a new drug submission (NDS), and the patient access program could be completed by the close of June.
“We are pleased to announce our plans to submit for review and to pursue early access options in Canada and will work to submit the NDS as swiftly as possible because we know that every day matters to people with ALS and their families,” Justin Klee, Amylyx’s co-CEO and co-founder, said in the release.
“Thank you to the entire ALS community who has helped bring this forward; your partnership is paramount,” Klee added.
Discussions between Amylyx and health authorities elsewhere are underway, regarding an appropriate path toward approval in their respective countries.
“Amylyx’s decision to pursue regulatory approval and a special access program is a promising milestone for the Canadian ALS community,” said Tammy Moore, CEO of the ALS Society of Canada.
“There is an urgent need for people living with ALS to have access to proven, effective therapies and we hope to see the momentum continue in meaningful ways that will make a difference to Canadians living with the disease,” Moore added.
AMX0035 combines two small molecules, tauroursodeoxycholic acid and sodium phenylbutyrate, that have been used in the clinic and are known to be safe and well tolerated.
These compounds work 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.
Amylyx’s decision to file for approval was based on positive clinical data from the multicenter CENTAUR Phase 2/3 trial (NCT03127514) and feedback from Health Canada.
CENTAUR evaluated AMX0035’s safety and effectiveness in 137 adults recently diagnosed with sporadic or familial ALS. All showed rapidly progressing disease — a stringent enrollment criteria meant to provide the most powerful results possible.
Participants were randomly assigned to an oral formulation of either AMX0035 (89 patients) or a placebo (48 patients) given twice daily for 24 weeks (about six months).
Most (92%) eligible patients who completed the trial 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 full data showed that the study met its main efficacy goal, with AMX0035-treated patients showing a clinically meaningful and statistically significant slowing of functional decline — as measured by the ALS Functional Rating Scale-Revised — than those on a placebo.
Notably, the therapy’s effect on disability progression was found to be independent of patients’ use of approved ALS treatments, and the duration of their use, before or during the trial.
In addition, long-term survival data spanning both CENTAUR and its extension study (nearly three years of follow-up) were presented at the Virtual 31st International Symposium on ALS/MND 2020.
Results here showed that patients initially assigned to AMX0035 lived significantly longer than those randomized to a placebo (25 months vs. 18.4 months), representing a 44% lower risk of death.
Moreover, an exploratory analysis using ENCALS, an ALS-specific survival prediction model that allows the comparison of participants’ actual vs. predicted survival, showed that AMX0035 was associated with a substantial survival benefit in these patients.
Those using AMX0035 since study’s start lived about a year (25 months) longer than predicted by the model (13.5 months), while those first given a placebo — including patients who moved to AMX0035 in the extension study — lived six months longer than predicted (18.4 vs. 12 months).
Importantly, there were no significant differences between actual and predicted survival among placebo group patients who chose not to enter the extension study and begin treatment with AMX0035.
AMX0035 was generally safe and well-tolerated, and associated with early, generally mild, gastrointestinal side effects.
“Results from CENTAUR demonstrated that AMX0035 has both functional and long-term survival benefits which were seen on top of baseline use of approved ALS therapies,” said Sabrina Paganoni, MD, PhD, the trial’s principal investigator with the Sean M. Healey & AMG Center for ALS at Mass General, in Boston. Paganoni is also an assistant professor at Harvard Medical School.
Angela Genge, MD, director of the clinical research unit at the Montreal Neurological Institute, in Quebec, said that these positive results “are encouraging for the approximately 3,000 Canadians living with ALS and their families who are desperately looking for effective treatment options.”
Based on CENTAUR findings, the ALS Association and I AM ALS filed a petition with the U.S. Food and Drug Administration in November, calling on the regulatory agency and Amylyx to make AMX0035 available to ALS patients as quickly as possible.
AMX0035 has been designated an orphan drug in both the U.S. and Europe. This status is meant to expedite the therapy’s development by providing regulatory support and financial benefits, as well as marketing exclusivity (seven years in the U.S. and 10 in Europe) upon approval.
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