Verdiperstat in Amyotrophic Lateral Sclerosis: Results From the Randomized HEALEY ALS Platform Trial

Area of Science:

• Neuroscience
• Pharmacology
• Clinical Trials

Background:

• Myeloperoxidase (MPO) is abundant in myeloid cells and linked to neuroinflammation and oxidative stress in ALS.
• MPO inhibitors offer potential therapeutic benefits for slowing neurodegeneration in ALS.

Purpose of the Study:

• To evaluate the safety, tolerability, and efficacy of verdiperstat, a selective MPO inhibitor, in patients with ALS.

Main Methods:

• A multicenter, double-blind, randomized clinical trial (HEALEY ALS Platform Trial) involving 167 adult participants with ALS.
• Participants received oral verdiperstat (600 mg twice daily) or placebo for 24 weeks.
• Primary outcome: change in disease severity using a joint model of ALS Functional Rating Scale-Revised and survival, quantified by disease rate ratio (DRR).

Main Results:

• The estimated DRR was 0.98 (95% credible interval, 0.77-1.24), indicating a 2% estimated slowing of progression versus placebo, with low probability (0.57) of disease modification.
• Verdiperstat was safe and well-tolerated, with common adverse events including nausea, insomnia, and elevated thyrotropin.
• The study included participants randomized from July 2020 to April 2022 across 54 US ALS referral centers.

Conclusions:

• Treatment with verdiperstat is unlikely to alter disease progression in patients with ALS.
• The findings suggest that targeting MPO with verdiperstat may not be an effective strategy for managing ALS progression.