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19-09-2023 | Amyotrophic Lateral Sclerosis | News

Phase 3 trial finds no clinical benefit with ravulizumab in ALS

Author: Dr. Jonathan Smith


medwireNews: Treatment with the terminal complement C5 inhibitor ravulizumab does not slow functional decline in patients with amyotrophic lateral sclerosis (ALS), the phase 3 CHAMPION-ALS trial shows.

“There was a clear rationale for testing ravulizumab as a treatment for ALS based on preclinical and clinical evidence suggesting that C5 may be involved in disease progression,” say James Berry (Massachusetts General Hospital, Boston, USA) and fellow investigators.

They note that the pharmacodynamic data from their trial showed that “C5 was immediately and completely inhibited in patients with ravulizumab,” but due to the futility criterion not being met at the 26-week interim analysis, the CHAMPION-ALS study was terminated.

The researchers randomly assigned 382 individuals with ALS to receive ravulizumab (n=255; mean age 58.6 years) or placebo (n= 127; mean age 58.0 years).

Ravulizumab was given intravenously at a loading dose of 2400 mg, 2700 mg, or 3000 mg, depending on weight, followed by maintenance doses of 3000 mg, 3300 mg, or 3600 mg on day 15 and every 8 weeks thereafter.

Most (60.2%) of the participants were men and the mean bodyweight was 73.8 kg. According to El Escorial criteria, 41.6% of patients had definite ALS, 17.8% had probable (laboratory supported), 31.2% had probable, and 9.4% possible ALS. At baseline, 87.2% and 14.1% of patients were taking riluzole or edaravone, respectively.

The preplanned futility analysis, carried out when 103 of the participants had completed week 26, showed that Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALASFRS-R) scores at week 50 had declined by a mean of 14.67 points among patients treated with ravulizumab, from a mean of 36.1 points at baseline. This was not significantly different to the mean 13.33-point reduction seen in the placebo group, from a starting point of 35.4 points.

This meant that the conditional power of the study was less than 0.1%, which was below the 10% futility threshold, and the trial was therefore terminated, the researchers explain.

Berry and colleagues note that a primary analysis conducted at week 50 also showed no significant benefit with ravulizumab for the Combined Assessment of Function and Survival score and there was no significant difference compared with placebo for secondary endpoints such as change in slow vital capacity and time to ventilation assistance-free survival.

There were no safety concerns, with treatment-emergent adverse events occurring in a similar proportion of patients in the ravulizumab and placebo groups, at 80% versus 85%.

“The outcomes of this randomized clinical trial indicate that unmet need remains regarding the treatment of people with ALS, as current disease management is mainly supportive and palliative,” write the investigators in JAMA Neurology. “Highly effective, novel treatments are critically needed to slow functional decline and extend survival in patients with ALS.”

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2023 Springer Healthcare Ltd, part of the Springer Nature Group

JAMA Neurol 2023; doi:10.1001/jamaneurol.2023.2851