After US approval, Amylyx faces regulatory hurdle in Europe for ALS treatment

Following a rocky and somewhat controversial road to securing a US Food and Drug Administration (FDA) approval, Amylyx’s amyotrophic lateral sclerosis (ALS) drug is likely to hit another regulatory snag in Europe.

AMX0035, marketed as Relyvrio in the US and Abrioza in Canada, is currently awaiting approval on its marketing authorisation application (MAA) from the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP).

However, the CHMP informed Amylyx that it was leaning toward issuing a negative opinion on its MAA, the company said in a 30 May release.

The CHMP is likely to issue the negative opinion next month. Tammy Sarnelli, Global Head of Regulatory Affairs and Clinical Compliance at Amylyx, stated that the company disagrees with CHMP’s current view and would request re-examination of the negative opinion if issued. If this is unsuccessful, an Amylyx spokesperson told Pharmaceutical Technology that the company would seek a new MAA based on the results of the PHOENIX study. Amylyx has completed the enrolment on the Phase III PHOENIX study (NCT05021536), being conducted across US and Europe, and topline results expected next year, as per a February release.

Relyvrio’s MAA is based on data from the Phase II CENTAUR clinical trial (NCT03127514), a randomized, multicenter, placebo-controlled trial in participants with ALS. The trial demonstrated a statistically significant benefit in function and an observed benefit on survival in a longer-term post hoc analysis. Relyvrio generally had similar reported rates of adverse events and discontinuations to placebo, with a slightly greater frequency of gastrointestinal events. However, experts were split on whether this data was sufficient for an approval, leading to the negative FDA advisory committee (AdCom) vote.

This latest disagreement is another chapter in the ongoing debate between regulators and pharmaceutical companies over ALS trial endpoints. ALSFRS-R is the preferred endpoint of most clinical studies, measuring function. However, the FDA prefers a joint-assessment of both function and survival that requires time-consuming data collection.

Amylyx found itself in the centre of this debate last year when the FDA approved Relyvrio after the negative vote from an advisory committee, in an unusual turn of circumstances. Contending with the stricter regulation of the EMA, this issue is unlikely to be settled anytime soon.

Despite an estimated 40,000 cases of ALS in Europe, new treatment options have been lacking. Riluzone, which was the last treatment approved for ALS over twenty years ago, is associated with an additional survival time of three months on average. Relyvrio in comparison has been shown to extend life by a median of ten months. ALS carries a poor prognosis, with most cases proving fatal in 3-5 years.