Verdiperstat Fails to Differentiate From Placebo in Critical HEALEY ALS Platform Trial


After previously failing a phase 3 trial of patients with multiple system atrophy, verdiperstat continued to show an effect in patients with ALS that was similar to those on placebo.

Irfan Qureshi, MD, senior vice president, Neurology, Biohaven Pharmaceuticals

Irfan Qureshi, MD

Verdiperstat, Biohaven’s investigational first-in-class potent, selective, brain-penetrant, irreversible myeloperoxidase (MPO) enzyme inhibitor, failed to statistically differentiate from placebo in newly announced findings from the pivotal HEALEY ALS Platform Trial (Master Protocol: NCT04297683), the first-ever platform trial in amyotrophic lateral sclerosis (ALS).1

In a brief company update, it was noted that the agent did not reach statistically significant differences on the prespecified primary outcome, disease progression, as measured by ALS Functional Rating Scale-Revised (ALSFRS-R), survival, and other key secondary measures. The safety profile of verdiperstat appeared to be similar to previous clinical trials. The full results of the study are expected to be presented at an upcoming scientific conference, according to Biohaven.

"We are incredibly grateful to our collaborators at the Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital, HEALEY ALS Platform Trial study investigators, and the ALS community—especially people with ALS and their families—who made the trial possible," Irfan Qureshi, MD, senior vice president, Neurology, Biohaven Pharmaceuticals, said in a statement.1 "While we are disappointed that verdiperstat did not demonstrate efficacy for ALS, Biohaven remains committed to developing treatments for people who suffer from neurodegenerative diseases."

In partnership with the Northeast ALS Consortium, this multicenter, double-blind, perpetual, adaptive platform trial tests multiple investigational products, including verdiperstat, in parallel, until effective treatments for ALS are found. The platform trial includes zilucoplan (RA Pharmaceuticals), CNM-Au8 (Clene Nanomedicine), pridopidine (Prilenia Therapeutics), and SLS-005 trehalose (Seelos Therapeutics), each of which are tested in individual placebo-controlled trials. Started in July 2020, the platform trial includes approximately 800 participants with ALS, and is expected to finalize in December 2023.

Of the 5 investigational agents being evaluated, regimen B included verdiperstat. This specific substudy (NCT04436510) of the platform trial included 160 participants with ALS who were randomly assigned 3:1 to either verdiperstat 600-mg oral tablet twice daily or placebo for 24 weeks. In addition to ALSFRS-R, other secondary end points included change in respiratory function, muscle strength, and survival.

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Clinical studies have shown that verdiperstat achieves peripheral target engagement and central target engagement in the brain; however, the recent HEALEY ALS trial failure is not the first for the agent. In September 2021, the MPO enzyme inhibitor failed to statistically differentiate itself from placebo on prespecified primary efficacy measures in the phase 3 M-STAR clinical trial (NCT03952806) of patients with multiple system atrophy (MSA).2

In that study, a total of 250 patients, aged 40 to 80 years, with MSA were randomly assigned 1:1:1 to verdiperstat 300 mg or 600 mg twice daily or placebo, with change in modified Unified MSA Rating Scale (UMSARS) as the primary end point. This primary outcome, observed over a 48-week treatment period, included a subset of items from the UMSARS Part 1 (Activities of Daily Living) and Part II (Motor Exam) that directly assessed clinically meaningful change in patients’ ability to function. These findings contrasted previous phase 2a findings, which showed favorable trends over 12 weeks on UMSARS with verdiperstat.3

1. Biohaven provies update from pivotal phase 2/3 trial with verdiperstat in amytophic lateral sclerosis (Healey ALS Platform trial). News release. Biohaven Pharmaceuticals. September 29, 2022. Accessed September 29, 2022.
2. Biohaven provides update on phase 3 trial and multiple system atrophy (MSA) program. News release. Biohaven Pharmaceuticals. September 27, 2021. Accessed September 29, 2021.
3. Biohaven’s verdiperstat receives orphan drug designation from FDA for multiple system atrophy. News release. Biohaven Pharmaceutical. February 19, 2019. Accessed September 29, 2022.
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