HEALEY Trial Fully Enrolled for 2 Regimens; Data Expected by Mid-2022
The HEALEY ALS platform trial, the first study to test several therapy candidates for amyotrophic lateral sclerosis (ALS) simultaneously, has completed enrollment for at least two of its first three regimens.
These include Clene Nanomedicine’s CNM-Au8 (NCT04414345) and Biohaven Pharmaceuticals’ verdiperstat (NCT04436510). The recruitment status for the other initial arm of the trial, UCB’s zilucoplan (NCT04436497), remains unclear, but all three regimens reached 50% of their target enrollment in March.
Pridopidine, being developed by Prilenia Therapeutics, was later added as the trial’s fourth arm (NCT04615923) — enrolling its first patient in January — while Seelos Therapeutics’ SLS-005 (trehalose) was cleared as the fifth regimen in September and its recruitment status is unknown.
The simultaneous evaluation of multiple potential therapies is meant to accelerate the identification and development of those showing the most promise, while reducing costs.
“We are grateful to people living with ALS, whose support and participation have made possible the completion of this critical milestone for this first-of-its-kind platform trial,” Merit Cudkowicz, MD, HEALEY’s principal investigator and sponsor, and director of the Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital (MGH), which is leading the trial, said in a press release.
“This achievement is pivotal for trial completion and result reporting, paving the way to continue groundbreaking research and find life-saving treatments for people with ALS,” added Cudkowicz, who is also chief of MGH’s neurology department and a professor of neurology at Harvard Medical School.
Robert Glanzman, MD, Clene’s chief medical officer, said that “by [boosting] cellular energy metabolism, we believe CNM-Au8 may improve outcomes for ALS patients who currently have few treatment options.”
Top-line results from the CNM-Au8 arm are expected in the second half of 2022, and should they be positive, Clene plans to use them shortly after to file an application with the U.S. Food and Drug Administration (FDA) seeking the therapy’s approval for ALS.
Researchers also anticipate top-line data from the verdiperstat arm by mid-2022 and, if positive, the data are expected to support the submission of a regulatory application with the FDA.
“Biohaven is very pleased that the verdiperstat arm of the trial is fully enrolled,” Irfan Qureshi, MD, the company’s vice president and verdiperstat development lead, said in a separate press release.
“People with ALS deserve novel and more effective therapeutic options,” and “this important milestone brings us closer to knowing whether verdiperstat can benefit people with ALS,” he added.
In each arm of the HEALEY platform trial (NCT04297683), 160 participants are randomly assigned to receive either the experimental therapy (120 patients) or a placebo (40 patients) for 24 weeks, or about six months. To strengthen the trial data, the placebo group will be shared between regimens.
The study’s main goal is to assess changes in ALS severity in patients over time, as measured by the ALS Functional Rating Scale-Revised. Secondary objectives include changes in respiratory function, muscle strength, and survival.
Recruiting patients at more than 50 sites across the U.S., HEALEY is designed to add clinical sites, participants, and treatment candidates until a cure for ALS is discovered.
“We celebrate the successful enrollment of the HEALEY ALS Platform Trial as it moves us closer to potential new treatment options for ALS,” Calaneet Balas, president and CEO of The ALS Association, said.
“The ALS Association is proud to support the trial and grateful to the HEALEY Center for championing this effort,” she added.
CNM-Au8 is an oral, liquid suspension of pure gold nanocrystals designed to increase energy production, while protecting cells against oxidative stress, which is an imbalance between the production of harmful free radicals and the cells’ ability to detoxify them.
Verdiperstat is an orally administered molecule that works by blocking myeloperoxidase, an enzyme believed to increase oxidative stress and inflammation levels in the brain and spinal cord.
Given that problems in mitochondria, oxidative stress, and inflammation have been associated with ALS, the therapies, both shown to reach the brain, may help to prevent nerve cell death and slow disease progression.
Recently announced top-line results from the RESCUE-ALS Phase 2 clinical trial (NCT04098406) showed that CNM-Au8 failed to prevent motor neuron loss and lung function decline in adults with early ALS.
However, the therapy significantly slowed disease progression and improved quality of life relative to placebo, while also showing potential to improve long-term survival. Meaningful benefits in additional secondary and exploratory measures were also observed in certain groups of patients.
ALS patients living in the U.S. and who are not eligible to enroll in HEALEY may gain early access to CNM-Au8 through an expanded access program launched in September by Clene, and its wholly owned subsidiary Clene Nanomedicine.