Relyvrio's failure laid bare in detailed PHOENIX readout

2024-04-17

临床结果临床3期上市批准

There were no surprises when results from the PHOENIX study of Amylyx Pharmaceuticals' ill-fated Relyvrio (sodium phenylbutyrate/taurursodiol) were presented at the American Academy of Neurology (AAN) annual meeting this week, but details from the confirmatory trial reveal the extent of how poorly the amyotrophic lateral sclerosis (ALS) drug performed.

Relyvrio was granted an accelerated approval by the FDA in 2022 based mainly on results from a small Phase II study that was criticised at the time by some of the agency’s scientists. Earlier this month, Amylyx said it would withdraw Relyvrio in the US – and in Canada where it was sold as Albrioza – making good on a promise to do so if the drug didn't succeed in the much-anticipated Phase III PHOENIX trial.

The study randomised 664 patients with clinically definite or clinically probable ALS within two years of symptom onset to receive either Relyvrio or placebo. The primary endpoint, change from baseline in ALS Functional Rating Scale-Revised (ALSFRS-R) total score at 48 weeks, dropped by an average of 14.98 points in the Relyvrio group versus 15.32 for placebo. The difference was not statistically significant.

The 137-patient CENTAUR study that supported the drug's approval had shown a difference of 2.32 points on the ALSFRS-R score in favour of Relyvrio versus placebo.

Meanwhile, PHOENIX also showed that Relyvrio had no significant benefit in key subgroups, including patients who were not on Mitsubishi Tanabe Pharma's Radicava (edaravone). Further, about a quarter of PHOENIX patients met enrolment criteria that was used in the CENTAUR trial – including having >60% slow vital capacity and being within 1.5 years of symptom onset – and while these patients fared better, the difference on ALSFRS-R was also not significant.

Trial investigator Leonard van den Berg said researchers will "continue to learn from PHOENIX to inform future ALS trials." Investigators are also still collecting survival data, but the full results for this secondary endpoint will not be available until 2025 or 2026. Subgroup analyses are also further evaluating "CENTAUR-like" patients in the study and comparing them to results from that trial.

For related analysis, see KOL Views Q&A: Leading neurologist outlines where ALS field goes next after Amylyx's Relyvrio failure.

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