Arimoclomol vs Placebo in Early ALS Does Not Improve Clinical Outcomes

Compared with placebo, arimoclomol did not improve efficacy outcomes among patients with early amyotrophic lateral sclerosis (ALS), according to study findings published in the Lancet Neurology.

Researchers conducted a multinational, randomized, double-blind, placebo-controlled, parallel-group trial (ORARIALS-01; ClinicalTrials.gov Identifier: NCT03491462) at 29 centers across 12 countries in Europe and North America to explore the safety and efficacy of arimoclomol in patients with ALS. Adults who met El Escorial criteria for clinically possible, probable, probable laboratory-supported, definite, or familial ALS; had an ALS Functional Rating Scale-Revised (ALSFRS-R) score of 35 or greater; and had slow vital capacity at 70% or more of the value predicted based on their age, sex, and height were eligible for inclusion. Patients were randomly assigned 2:1 to receive oral arimoclomol citrate 1200 mg/day (400 mg administered 3 times per day) or placebo, with or without a stable background dose of riluzole.

The primary outcome was the Combined Assessment of Function and Survival (CAFS) rank score over the course of 76 weeks of treatment, which was analyzed using Gehan extension of the Wilcoxon rank test. Cox proportional hazards models were also used in statistical analysis.

A total of 239 patients comprised the modified intention-to-treat population, 160 (mean age, 58.0; men, 66%; White, 85%) of whom were randomly assigned to receive arimoclomol and 79 (mean age, 56.6; men, 57%; White, 84%) of whom were randomly assigned to receive placebo.

The mean CAFS rank score over 76 weeks of treatment for patients in the arimoclomol and placebo groups was 0.51 and 0.49, respectively. There was no significant difference in the treatment effect as estimated by Cliff delta value 0.039 (95% CI, -0.116 to 0.194; P =.062).

No significant between-group differences were observed for any of the secondary endpoints, which included time to permanent assisted ventilation, tracheostomy, or death, as well as change from baseline over 76 weeks in slow vital capacity and ALSFRS-R score.

The incidence of adverse events (AEs), serious AEs, and fatal AEs was similar between treatment groups. Compared with the placebo group, the arimoclomol group experienced more AEs that led to treatment discontinuation (26 vs 4, respectively) and more AEs that were related to treatment (104 vs 41, respectively).

A total of 29 and 18 patients in the arimoclomol and placebo groups, respectively, died. Most deaths were attributable to disease progression.

Study limitations included the impact of the COVID-19 pandemic and lack of biomarker data from the phase 2 trial.

“Based on the results of this trial, arimoclomol does not warrant further investigation

as a potential therapeutic for patients with amyotrophic lateral sclerosis,” the researchers concluded.

Disclosures: This research was supported by Orphazyme. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.