Verdiperstat in Amyotrophic Lateral Sclerosis: Results From the Randomized HEALEY ALS Platform Trial
Recommended Citation
Andrews J, Paganoni S, Macklin EA, Chibnik LB, Quintana M, Saville BR, Detry MA, Vestrucci M, Marion J, McGlothlin A, Young E, Chase M, Pothier L, Harkey B, Yu H, Sherman A, Shefner J, Hall M, Kittle G, Connolly MR, Berry JD, D'Agostino D, Tustison E, Giacomelli E, Scirocco E, Alameda G, Locatelli E, Ho D, Quick A, Heitzman D, Ajroud-Driss S, Appel SH, Shroff S, Katz J, Felice K, Maragakis NJ, Simmons Z, Goutman SA, Olney N, Miller T, Fernandes JA, Ilieva H, Jawdat O, Weiss MD, Foster L, Vu T, Ladha S, Owegi MA, Newman DS, Arcila-Londono X, Jackson CE, Swenson A, Heiman-Patterson T, Caress J, Fee D, Peltier A, Lewis R, Rosenfeld J, Walk D, Johnson K, Elliott M, Kasarskis EJ, Rutkove S, McIlduff CE, Bedlack R, Elman L, Goyal NA, Rezania K, Twydell P, Benatar M, Glass J, Cohen JA, Jones V, Zilliox L, Wymer JP, Beydoun SR, Shah J, Pattee GL, Martinez-Thompson J, Nayar S, Granit V, Donohue M, Grossman K, Campbell DJ, Qureshi IA, Cudkowicz ME, and Babu S. Verdiperstat in Amyotrophic Lateral Sclerosis: Results From the Randomized HEALEY ALS Platform Trial. JAMA Neurol 2025; 82(4):333-343.
Document Type
Article
Publication Date
4-1-2025
Publication Title
JAMA Neurol
Abstract
IMPORTANCE: 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.
OBJECTIVE: To determine the safety, tolerability, and efficacy of verdiperstat, a selective myeloperoxidase inhibitor, in ALS.
DESIGN SETTINGS AND PARTICIPANTS: 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.
INTERVENTIONS: 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.
MAIN OUTCOMES AND MEASURES: 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-Revised 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.
RESULTS: 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 = 0.57 for slowing of disease progression [DRR < 1]). Verdiperstat was estimated to slow progression by 2% vs placebo (95% credible interval, -23% 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.
CONCLUSIONS AND RELEVANCE: Results demonstrate that treatment with verdiperstat was unlikely to alter disease progression in ALS.
TRIAL REGISTRATION: Clinical Trial Identifiers: NCT04297683 and NCT04436510.
Medical Subject Headings
Adult; Aged; Female; Humans; Male; Middle Aged; Amyotrophic Lateral Sclerosis; Double-Blind Method; Enzyme Inhibitors; Treatment Outcome
PubMed ID
40067754
ePublication
ePub ahead of print
Volume
82
Issue
4
First Page
333
Last Page
343
