ALS Therapy Verdiperstat Fails to Meet Efficacy Goals in HEALEY Trial

Biohaven candidate did not slow functional decline or improve survival

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Biohaven‘s therapy candidate verdiperstat did not significantly slow functional decline among people with amyotrophic lateral sclerosis (ALS) in the HEALEY ALS platform trial, failing to meet its primary goal, data show.

Key secondary efficacy goals, such as survival and changes in lung function and muscle strength, also were not met after six months of treatment. Additional analyses are still ongoing; Biohaven plans to present complete results at an upcoming meeting.

“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,” Irfan Qureshi, MD, senior vice president of neurology at Biohaven, a wholly-owned subsidiary of Pfizer, said in a company press release.

Biohaven did not immediately reveal its plans for verdiperstat moving forward.

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HEALEY is the first trial to evaluate verdiperstat for ALS, but the investigational treatment last year similarly failed to meet its primary goal in a trial for multiple system atrophy (MSA), another quickly progressing neurological condition. That Phase 3 trial (NCT03952806) was testing verdiperstat’s ability to slow disease progression in MSA.

The HEALEY platform (NCT04297638) — a “perpetual multi-center, multi-regimen clinical trial” —  was designed to simultaneously evaluate several investigational ALS therapies against a shared placebo group. The overall trial, which is still recruiting participants, is expected to speed the development of new treatments while cutting costs.

In addition to verdiperstat (NCT04436510), active trial arms include Prilena Therapeutic’s pridopidine (NCT04615923), Clene Nanomedicine’s CNM-Au8 (NCT04414345) and Seelos Therapeutics’ SLS-005 (NCT05136885).

A fifth regimen, for UCB’s zilucoplan (NCT04436497), was discontinued earlier this year due to a lack of effectiveness in an interim analysis.

Verdiperstat trial for ALS

All trial arms, which are being conducted at more than 65 sites in the U.S., are led by the Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital, in Boston, under the direction of Merit Cudkowicz, MD.

Verdiperstat is an orally administered inhibitor of the myeloperoxidase (MPO) enzyme, which is thought to increase oxidative stress and inflammation levels in the brain and spinal cord — two processes that have been implicated in ALS. By suppressing MPO’s activity, verdiperstat was expected to ease these damaging processes and slow disease progression.

The treatment was originally developed by AstraZeneca and licensed to Biohaven in 2018.

HEALEY’s verdiperstat arm enrolled 167 participants who were randomly assigned to receive the active treatment (600 mg) or a placebo, twice daily for 24 weeks, or about six months. Patients were randomized in a 3:1 ratio, meaning that for each patient assigned a placebo, three were given verdiperstat.

The trial’s main goal was to assess whether verdiperstat could slow disease progression, as measured by changes in the ALS Functional Rating Scale Revised (ALSFRS-R). Secondary goals included changes in lung function, muscle strength, and survival.

Safety data were consistent with findings from previous clinical trials. However, the treatment failed to meet both its primary and key secondary goals, with results that “did not statistically differentiate from placebo,” 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,” Qureshi said.

Results from the CNM-Au8 trial also were shared recently by Clene Nanomedicine. Like verdiperstat, CNM-Au8 failed to meet its primary and secondary goals. It aimed to slow lung function decline in people with ALS.

However, top-line data showed that therapy significantly reduced the risk of death, and the risk of death and permanent assisted ventilation, by more than 90%.

HEALEY is designed to continue adding new experimental therapeutics until a cure for ALS is found. Potential new regimens are evaluated by a committee comprised of ALS experts and members of the Healey Center Science Advisory Committee.

ABBV-CL-7262, an investigational oral treatment from AbbVie and Calico Life Sciences, will likely be the sixth therapy to be added to the platform trial.