EMA Favors Giving Amylyx’s AMX0035 Orphan Medicine Status for ALS

A branch of the European Medicines Agency (EMA) has recommended that Amylyx‘s investigational oral compound AMX0035 be designated an orphan medicine to treat people with amyotrophic lateral sclerosis (ALS).

Orphan designation is given to medicines in Europe with the potential to be safe and effective treatments for rare, life-threatening or chronically debilitating conditions affecting no more than 1 every in 2,000 people. It provides companies with a range of incentives, including assistance with trial protocols and a 10-year period of market exclusivity should the treatment is approved.

The positive opinion by the Committee for Orphan Medicinal Products (COMP) puts AMX0035 closer to such incentives in Europe, and follows an orphan drug designation granted it by the U.S. Food and Drug Administration (FDA) in 2017 for the same indication. A final decision on COMP opinions is made by the European Commission.

“ALS patients worldwide are in need of new therapies,” Joshua Cohen, co-CEO, chairman, and co-founder of Amylyx, said in a press release. “We’re excited about today’s news and look forward to working with the European Medicines Agency on the next steps for AMX0035.”

AMX0035 is a combination therapy that includes two small molecules — tauroursodeoxycholic acid and sodium phenylbutyrate — both of which act to prevent nerve cell death by blocking stress signals in cells.

This potential treatment does not target the root cause of ALS. Rather, AMX0035 aims to preserve the motor neurons that are progressively lost in ALS patients, causing clinical decline.

AMX0035 was investigated in a double-blind Phase 2 safety and efficacy trial, called CENTAUR (NCT03127514), in 137 ALS patients diagnosed within eight months of enrolling and with rapidly progressive disease.

At 25 clinical centers across the U.S., patients were randomly assigned to either AMX0035 or placebo, given twice daily for six months. While in the trial, they could continue with their stable riluzole treatment.

After completing this trial, all were given the option to enter an open-label extension study and receive the experimental treatment for an additional 30 months. About 90% of patients, around 120 people, opted to enter in CENTAUR-OLE (NCT03488524).

Amylyx announced in December that CENTAUR met its primary goal, with patients randomized to AMX0035 experiencing a slower decline in existing abilities, including speech, swallowing, dressing and hygiene, compared with those on a placebo.

This was measured by changes from baseline in ALS Functional Rating Scale-Revised (ALSFRS-R) scores. Details on these scores between these two patient groups have not yet been released.

CENTAUR is also assessing AMX0035’s safety and tolerability as primary goals. Secondary efficacy measures being evaluated include the therapy’s impact on muscle strength, respiratory function, and biomarkers of ALS. Survival, hospital admissions, and the need for breathing tubes will also be measured.

Amylyx is planning to publish CENTAUR’s findings in a medical journal in the near future.

AMX0035 is also being studied as a potential Alzheimer’s treatment in the Phase 2 PEGASUS trial (NCT03533257) due to conclude in December.