CHMP confirms its initial position against approving AMX0035 in EU

Top-line data from Phase 3 PHOENIX trial are expected by June 2024

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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An advisory committee of the European Medicines Agency has maintained its recommendation not to approve AMX0035 for amyotrophic lateral sclerosis (ALS).

In its initial assessment issued in June, the Committee for Medicinal Products for Human Use (CHMP) said data from the CENTAUR Phase 2 trial (NCT03127514), which formed the basis for the application, did not convincingly show that AMX0035 was effective at slowing ALS progression.

Amylyx Pharmaceuticals, the company developing the treatment, then requested a formal re-examination, in which available clinical data were evaluated by a different set of examiners, but this second review process has confirmed the initial opinion.

An official decision on AMX0035 from the European Medicines Agency is now set to be handed down by year’s end. The regulatory agency is not obligated to abide by the committee’s opinion, but it usually does.

“We are disappointed to learn of this outcome, as it is a further setback for the more than 30,000 people living with ALS and their loved ones in Europe who have not seen therapeutic progress for this devastating disease in over 25 years,” the patients and carers board of the European Organization for Professionals and Patients with ALS said in a press release.

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Other paths to AMX0035’s approval in Europe being explored

Meanwhile, the company says it will continue to explore other paths to AMX0035’s approval in Europe.

The treatment is being evaluated in a larger Phase 3 trial called PHOENIX (NCT05021536), whose data was not included in the initial application. Pending positive results, Amylyx is planning to submit an application to the European agency as soon as possible.

AMX0035, a fixed-dose combination of tauroursodeoxycholic acid and sodium phenylbutyrate, is already available in the U.S. under the brand name Relyvrio. It has also gained conditional approval in Canada, where it is sold as Albrioza — that brand name will also be used in Europe if it’s approved.

“We share the frustration felt by the European ALS community, who has no time to wait for new, safe, and effective treatment options,” said Stéphanie Hoffmann-Gendebien, general manager and head of Europe, the Middle East, and Africa at Amylyx.

“We remain committed to exploring all potential paths forward in support of the company’s goal of getting AMX0035 to people living with ALS in the EU as quickly as possible,” she added.

The safety and effectiveness of AMX0035 was initially assessed in the CENTAUR trial, which enrolled 137 adults with early and rapidly progressing ALS. Data showed Relyvrio significantly slowed functional decline and extended survival, compared with a placebo.

“AMX0035 is the first and only drug to show an effect on both function and survival in the same trial. Since the medication’s approval with conditions in Canada and full approval in the U.S., thousands of people have been prescribed AMX0035 in North America,” said Joshua Cohen and Justin Klee, co-CEOs of Amylyx.

We are disappointed to learn of this outcome, as it is a further setback for the more than 30,000 people living with ALS and their loved ones in Europe who have not seen therapeutic progress for this devastating disease in over 25 years.

Phase 3 PHOENIX trial fully enrolled with 664 participants in US, Europe

The PHOENIX trial was then launched to confirm the benefits seen in CENTAUR in a larger group of ALS patients. The trial is fully enrolled, with 664 participants recruited across 69 clinical sites in the U.S. and Europe.

Participants were randomly assigned to Relyvrio or a placebo, given daily for 48 weeks, or nearly one year. They will then be given the option to join an open-label extension part, where all will the receive the medication for two years.

The trial’s main goal is to determine if AMX0035 can slow disease progression, as assessed by changes in the ALS Functional Rating Scale-Revised (ALSFRS-R). Secondary measures include changes in lung function and quality of life, and an extension in survival time.

Top-line data are expected by June 2024.

“ALS has no geographical boundaries, and we are working with urgency toward providing timely, broad, and sustainable access to AMX0035 for eligible people living with ALS who may benefit,” Cohen and Klee added.