New EAP will allow pridopidine use for ALS patients not in trial

NIH grant will support expanded access program for Prilenia therapy

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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Amyotrophic lateral sclerosis (ALS) patients not eligible to participate in clinical trials of pridopidine — a small molecule developed by Prilenia Therapeutics to slow disease progression in ALS — will soon be able to receive the experimental therapy via an expanded access program (EAP).

EAPs, also known as compassionate-use programs, are aimed at people with serious or life-threatening conditions that have few or no adequate treatments. Such programs allow patients to access investigational therapies available outside of a clinical trial. They typically run in parallel with late-stage clinical trials and provide additional clinical data that may support an approval of the given treatment by regulatory agencies.

Led by researchers at the Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital in collaboration with Prilenia, this EAP will enroll about 200 patients at as many as 45 centers across the U.S. Participants will receive the medication for up to two years.

The program is being launched thanks to a grant from the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health (NIH), and is supported by the Accelerating Access to Critical Therapies (ACT) for ALS act.

“Prilenia is proud to work together with The Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital to make this important EAP possible for the many people living with more advanced stages of ALS,” Michael R. Hayden, Prilenia’s founder and CEO, said in a press release, adding, “We share the great appreciation for the NIH and NINDS for supporting this work through the Act for ALS.”

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EAP for pridopidine expected to provide real world data

In the release, the Healey & AMG Center staff said the expanded access program “will provide real world safety, biomarker, and clinical data in two hundred (200) ALS individuals treated with pridopidine for up to two (2) years, thus contributing to our understanding of the effects of pridopidine in a broad population.”

The EAP’s lead investigators are Suma Babu, an assistant professor of neurology at Harvard Medical School, James Berry, MD, director of Massachusetts General Hospital’s Neurological Clinical Research Institute, and Sabrina Paganoni, MD, PhD, a physician-scientist at the Healey Center and co-director of the Neurological Clinical Research Institute.

“We are grateful to the NIH for this award, and the opportunity to launch the pridopidine EAP,” Babu, Berry, and Paganoni said, adding, “Programs like this help advance research and innovation in ALS.”

Pridopidine is an orally available small molecule designed to bind and activate the sigma-1 receptor (S1R), a protein that’s broadly produced in the brain and spinal cord and regulates a number of processes needed for nerve cell function and survival.

By activating S1R, the therapy boosts the clearance of toxic molecules, increases energy production, and limits inflammation and cellular stress — all known hallmarks of ALS. In doing so, the therapy is expected to ease certain disease mechanisms, thereby slowing disease progression.

We are grateful to the NIH for this award, and the opportunity to launch the pridopidine EAP. … Programs like this help advance research and innovation in ALS.

The candidate therapy was the focus of one arm of the HEALEY ALS Platform trial (NCT04297683) — a study testing multiple potential ALS therapies at the same time against a shared placebo group. The study was led by the Healey Center.

Pridopidine’s Phase 2/3 trial arm (NCT04615923) enrolled 163 adults with ALS, whose symptoms had started less than three years before screening. Each was randomly assigned to receive either oral pridopidine, at a dose of 45 mg, or a placebo, twice daily for 24 weeks, or about six months.

The trial ultimately failed to meet its primary goal of showing that pridopidine could significantly slow disease progression, as measured by changes in the ALS Functional Rating Scale-Revised (ALSFRS-R), a standardized measure that assesses a patient’s ability to perform daily activities.

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There were significant benefits seen in certain speech measures in participants given pridopidine, however, as well as positive trends in respiratory function for these patients.

The medication also showed promising trends in a subgroup of patients with rapidly progressing disease, all of whom were enrolled less than 18 months after symptom onset.

In this group, pridopidine-treated patients had a significantly smaller decline in ALSFRS-R scores than those given the placebo (7.5 vs. 12.7). These patients also had an average 40% reduction in neurofilament light chain (NfL) levels, a marker or nerve damage, compared with patients given the placebo.

Based on these findings, Prilenia has decided to move pridopidine into Phase 3 clinical trials.

Participants also are being followed in the trial’s open-label extension, in which all are receiving the experimental therapy. Data from this open-label part and from the upcoming EAP may help to better understand the effects of pridopidine in ALS patients.

“We … want to express our gratitude to the participants and their families as well as the site healthcare providers and staff who will make this EAP possible, further advancing our understanding of pridopidine as a potential therapy for ALS,” Hayden said.

Pridopidine has been granted orphan drug designation for ALS in both the U.S. and Europe. This designation aims to encourage therapies for rare and serious diseases, through benefits such as market exclusivity and exemption from certain fees.