Functional and survival benefits of AMX0035 in ALS

AMX0035, aimed at decreasing neuronal cell death, significantly reduced the risk of death in amyotrophic lateral sclerosis (ALS) patients compared with placebo, regardless of concomitant use of riluzole and/or edaravone. This was the result of the long-term survival analysis of the phase 2 CENTAUR trial. The study used a novel approach of collecting survival data.

AMX0035 is an oral, fixed-dose combination of 2 compounds (sodium phenylbutyrate and taurursodiol), which decreases neuronal cell death. The phase 2 CENTAUR trial (NCT03127514) included 137 patients, who were randomised 2:1 to AMX0035 or placebo. After 6 months, the primary safety, tolerability, and efficacy endpoints (ALSFRS-R slope reduction of 2.32 points) were met. Subsequently, 92% of participants entered the open-label extension (OLE). Long-term survival data was collected through a participant-locating service, a method new to ALS trials [1]. In this way, survival data could be retrieved from all original participants. Results were presented by Dr Sabrina Paganoni (Massachusetts General Hospital, MA, USA).

Participants originally randomised to AMX0035 had a 44% lower risk of death than participants in the placebo group (HR 0.56; 95% CI 0.34–0.92; P=0.023), with corresponding improved median survival (25.0 vs 18.5 months) and median duration of exposure (8.8 vs 1.9 months). Dr Paganoni emphasised that these results were obtained despite all participants already using riluzole and/or edaravone at baseline. Participants in the AMX0035 group survived longer without tracheostomy, permanent assisted ventilation, and first hospitalisation. Dr Paganoni added that the true impact of AMX0035 on survival may be underestimated, since many participants in the original placebo group were exposed to AMX0035 in the OLE. An exploratory analysis suggested that the placebo group had a 6.4-month longer median survival than predicted, suggesting a higher long-term survival benefit of AMX0035.

1. Paganoni S, et al. Long-Term Survival of Participants in the CENTAUR Trial of AMX0035 for ALS. AAN 2021 Virtual Congress, 17-22 April.

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Posted on 16 June 202122 February 2024