Verdiperstat use may not impact progression of amyotrophic lateral sclerosis: JAMA

A new study published in the recent issue of Journal of American Medical Association found that the usage of verdiperstat, a selective myeloperoxidase inhibitor, had no effect on the course of amyotrophic lateral sclerosis (ALS).

One of the most prevalent peroxidase enzymes in activated myeloid cells is myeloperoxidase. By reducing oxidative stress and neuroinflammation, myeloperoxidase inhibitors may halt neurodegeneration in amyotrophic lateral sclerosis. Thus, this research was set to evaluate the effectiveness, safety and tolerability of verdiperstat in treating ALS.

The HEALEY ALS Platform Trial is a double-blind, ticenter, randomized clinical trial, platform design which examined verdiperstat as a regimen. From July 2020 to April 2022, the study was carried out at 54 ALS referral sites around the United States. Verdiperstat or a regimen-specific placebo was randomly assigned to adult volunteers diagnosed with clinically plausible, likely, laboratory-supported probable, or definite ALS according to the updated El Escorial criteria.

The analysis also included a second group of patients who were concurrently assigned to placebo from various regimens. For a planned placebo-controlled period of 24 weeks, eligible subjects were randomized in a 3:1 ratio to receive oral verdiperstat, 600 mg, twice daily, or a matched placebo.

A joint model of the ALS Functional Rating Scale–Revised and survival was used to measure the primary efficacy outcome, which was the change in disease severity from baseline through week 24. The disease rate ratio (DRR) was used to quantify the treatment effect; a DRR of less than 1 indicated that verdiperstat was slowing the progression of the disease in comparison to a placebo.

This study randomized 167 subjects to either verdiperstat or regimen-specific placebo. A total of 130 people (78%) who were randomly assigned to the verdiperstat regimen finished the experiment. The DRR was predicted to be 0.98.

When compared to a placebo, verdiperstat was projected to decrease development by 2%. Overall, verdiperstat was well accepted and safe. In the verdiperstat group, nausea, sleeplessness, and increased thyrotropin levels were frequent side effects. Overall, the results of this trial revealed that the use of verdiperstat did not impact the progression of the disease in patients with amyotrophic lateral sclerosis.

Reference:

Writing Committee for the HEALEY ALS Platform Trial, HEALEY ALS Platform Trial Study Group. Verdiperstat in Amyotrophic Lateral Sclerosis: Results From the Randomized HEALEY ALS Platform Trial. JAMA Neurology. Published online February 17, 2025. https://doi.org/10.1001/jamaneurol.2024.5249