HEALEY ALS platform trial launches new arm testing oral therapy NUZ-001
Ninth regimen, I, expects to enroll 160; first patient now dosed
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The HEALEY ALS Platform Trial has launched a new arm, called Regimen I, that's testing the oral therapy NUZ-001 for ALS.
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NUZ-001, originally a veterinary drug, aims to slow declines in physical function and improve survival in ALS.
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An early trial showed NUZ-001 was safe and well-tolerated among patients.
Dosing has begun in a new arm of the HEALEY ALS platform trial, with Regimen I — the ninth — testing NUZ-001, an oral small molecule developed by Neurizon Therapeutics to slow declines in function and extend survival in people with amyotrophic lateral sclerosis (ALS).
As a platform trial, HEALEY ALS (NCT04297683) is designed to test multiple experimental therapies simultaneously using a shared protocol and placebo group. This setup is expected to reduce costs and accelerate the development of new treatments for ALS.
NUZ-001 was cleared to enter the platform trial late last year, becoming the ninth regimen to join the study: Regimen I.
“The dosing of the first participant in Regimen I of the HEALEY ALS Platform Trial marks a defining milestone for Neurizon and for NUZ-001,” Michael Thurn, PhD, Neurizon’s managing director and CEO, said in a company press release announcing that patient dosing has started.
“This study represents our registrational trial in ALS — a rigorous, adaptive Phase 2/3 program designed to generate the clinical evidence required to support potential regulatory submissions,” Thurn said.
According to the developer, the NUZ-001 Phase 2/3 arm (NCT07410806) will enroll an estimated 160 patients at ALS clinical centers across the U.S.
Participants in Regimen I will be randomly assigned to receive NUZ-001 (10 mg/kg) or a placebo, daily for 36 weeks, or about eight months. Participants will be randomized in a 3:1 ratio, meaning that for each patient given a placebo, three will receive the active treatment.
After completing the main trial, patients may enter an extension phase in which all will receive NUZ-001.
Trial arm will test NUZ-001 impact on physical function, survival
The main goal of this trial arm is to assess changes in scores on the ALS Functional Rating Scale-Revised (ALSFRS-R), a standard measure of physical function in ALS, as well as survival, over the 36-week treatment period. Researchers will also monitor additional clinical outcomes and continue tracking safety.
The developer was welcomed to the platform trial by Merit Cudkowicz, MD, its principal investigator.
“We look forward to working with Neurizon on this new regimen in the HEALEY ALS Platform Trial,” Cudkowicz said. “Beginning [enrollment] is a significant step for the regimen, and would not be possible without the dedication of people living with ALS and their families, collaborators, and our top trials sites.”
NUZ-001, previously known as monepantel, is an oral small molecule that was originally developed to treat parasitic worm infections in livestock. However, researchers have found that it also has an off-target effect on the mTOR signaling pathway, which helps regulate a cellular process called autophagy. Through autophagy, unneeded or damaged components are broken down and recycled.
Autophagy is disrupted in ALS, contributing to the buildup of misfolded proteins that are thought to drive nerve cell damage and death among patients. By blocking mTOR, NUZ-001 may help reduce the buildup of misfolded proteins and potentially slow the progression of ALS, according to the developer.
Entry into the HEALEY ALS Platform Trial reflects our scientific data package and the favourable safety and tolerability profile observed in our Phase 1 and open label extension studies.
Data from a small dose-finding Phase 1 clinical trial (NCT04894240) and its open-label extension (NCT06177431) showed daily treatment with NUZ-001 was generally safe and well tolerated. Compared with historical data, patients treated with NUZ-001 lived longer and experienced slower functional decline. The therapy was also linked to slower declines in lung function.
“Entry into the HEALEY ALS Platform Trial reflects our scientific data package and the favourable safety and tolerability profile observed in our Phase 1 and open label extension studies,” Thurn said.
NUZ-001 was selected for HEALEY in 2024
The HEALEY ALS Platform Trial is led by the Sean M. Healey & AMG Center for ALS at Mass General Brigham, in partnership with the Network of Excellence in ALS. It is enrolling participants across more than 70 U.S. locations.
The trial continuously adds new treatment candidates, which must undergo extensive expert review before being accepted onto the platform. NUZ-001 was selected for inclusion in 2024 by a group of ALS experts and members of the Healey & AMG Center Science Advisory Committee.
“We are advancing NUZ-001 with scientific discipline, operational focus, and deep respect for the ALS community,” Thurn added. “We are deeply grateful to the participants and their families who commit their time and energy to clinical research, often while navigating the significant challenges associated with living with ALS. For people living with ALS, urgency matters.”
