{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T19:23:53Z","timestamp":1793388233981,"version":"4.5.0"},"reference-count":27,"publisher":"American Medical Association (AMA)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Neurol"],"published-print":{"date-parts":[[2025,4,1]]},"abstract":"Importance<\/jats:title>Myeloperoxidase is one of the most abundant peroxidase enzymes in activated myeloid cells. Myeloperoxidase inhibitors may have a clinical benefit in amyotrophic lateral sclerosis (ALS) by slowing neurodegeneration via reduced neuroinflammation and oxidative stress.<\/jats:p><\/jats:sec>Objective<\/jats:title>To determine the safety, tolerability, and efficacy of verdiperstat, a selective myeloperoxidase inhibitor, in ALS.<\/jats:p><\/jats:sec>Design, Settings, and Participants<\/jats:title>Verdiperstat was tested as a regimen of the HEALEY ALS Platform Trial, a multicenter, double-blind, perpetual platform design, randomized clinical trial, with sharing of trial infrastructure and placebo data across multiple regimens. The study was conducted at 54 ALS referral centers across the US from July 2020 to April 2022. Adult participants with a diagnosis of clinically possible, probable, laboratory-supported probable, or definite ALS defined by the revised El Escorial criteria were randomized to verdiperstat or regimen-specific placebo. An additional group of participants concurrently randomized to placebo from other regimens was included in the analyses.<\/jats:p><\/jats:sec>Interventions<\/jats:title>Eligible participants were randomized in a 3:1 ratio to receive oral verdiperstat, 600 mg, twice daily or matching placebo for a planned placebo-controlled duration of 24 weeks.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>The primary efficacy outcome was change from baseline through week 24 in disease severity, as measured by a joint model of ALS Functional Rating Scale\u2013Revised and survival, with the treatment effect quantified by the disease rate ratio (DRR), with DRR less than 1 indicating a slowing in disease progression of verdiperstat relative to placebo.<\/jats:p><\/jats:sec>Results<\/jats:title>A total of 167 participants (mean [SD] age, 58.5 [11.4] years; 59 [35.3%] female; 108 [64.6%] male) were randomized to either verdiperstat (126 [75.4%]) or to placebo (41 [25.6%]). Among the participants randomized to the verdiperstat regimen, 130 (78%) completed the trial. The estimated DRR was 0.98 (95% credible interval, 0.77-1.24; posterior probability\u2009=\u20090.57 for slowing of disease progression [DRR &amp;lt;1]). Verdiperstat was estimated to slow progression by 2% vs placebo (95% credible interval, \u221223% to 24%; posterior probability 0.57). Verdiperstat was overall safe and well tolerated. Common adverse events in the verdiperstat group were nausea, insomnia, and elevated thyrotropin levels.<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>Results demonstrate that treatment with verdiperstat was unlikely to alter disease progression in ALS.<\/jats:p><\/jats:sec>Trial Registration<\/jats:title>Clinical Trial Identifiers: NCT04297683<\/jats:ext-link> and NCT04436510<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1001\/jamaneurol.2024.5249","type":"journal-article","created":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T16:32:49Z","timestamp":1739809969000},"page":"333","source":"Crossref","is-referenced-by-count":20,"title":["Verdiperstat in Amyotrophic Lateral Sclerosis"],"prefix":"10.1001","volume":"82","author":[{"name":"Writing Committee for the HEALEY ALS Platform Trial","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas * 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