New HEALEY trial analyses further show CNM-Au8’s survival benefits
Gains longer in patients meeting Phase 3 RESTORE-ALS enrollment criteria
Treatment with CNM-Au8 in the HEALEY ALS platform trial prolonged survival for people with amyotrophic lateral sclerosis (ALS) relative to those who received the investigational treatment zilucoplan or a placebo in a separate arm of the study, according to new analyses.
The benefits were most pronounced in the subgroup who meet the enrollment criteria for the planned confirmatory Phase 3 RESTORE-ALS trial, set to launch mid-year. CNM-Au8’s developer Clene plans to seek accelerated approval of CNM-Au8 for ALS later this year, which will require that RESTORE-ALS be underway.
“We are highly encouraged by these results, as the significant survival advantage demonstrated by CNM-Au8 not only reinforces its potential to extend life for people living with ALS, but also validates our strategic direction as we prepare for the launch of our confirmatory Phase 3 RESTORE-ALS study in mid-2025,” Rob Etherington, president and CEO of Clene, said in a company press release. “We look forward to discussing these findings with the [U.S. Food and Drug Administration] as we advance toward commercialization.”
HEALEY ALS (NCT04297683) is designed to simultaneously test multiple investigational treatments in ALS patients against a shared placebo group in order to accelerate treatment development and cut costs. Each arm has the same recruitment criteria and is designed similarly, with about 75% of participants assigned to receive the experimental treatment and 25% the shared placebo group. For all the arms, the main goal is to evaluate a treatment’s ability to slow ALS progression and prolong survival after six months.
CNM-Au8 is a liquid suspension of gold nanocrystals intended to support the energetic needs of nerve cells, improving their health and helping them survive. In its own arm of the HEALEY trial (NCT04414345), 161 ALS patients were randomly assigned to receive CNM-Au8 at either of two daily doses — 30 mg or 60 mg — or a placebo.
While CNM-Au8 didn’t significantly slow functional declines relative to a placebo, the 30 mg dose was associated with a reduced risk of death or clinical worsening after six months. A survival benefit relative to an external group of placebo-treated patients was also demonstrated in the study’s long-term open-label extension.
Regimen A (NCT04436497) of the HEALEY trial tested zilucoplan, but was stopped early after interim data indicated a lack of efficacy. The long-term survival status of participants was still tracked, with no difference observed between those given the treatment versus a placebo.
Comparing long-term benefits
In the recent analysis, scientists compared the long-term survival of 59 HEALEY participants given 30 mg of CNM-Au8 with that of 162 participants from Regimen A, combining both zilucoplan- and placebo-treated patients since there was no survival difference between them. Most participants in either group (78%) were receiving standard ALS treatments, including riluzole as Rilutek, edaravone as Radicava, or both, at the study’s start. Long-term survival data were collected for up to 48 months, or four years.
The median survival with CNM-Au8 was 951 days, or more than 2.5 years, compared with 753 days in Regimen A, amounting to about a 6.5 month benefit with CNM-Au8.
In an analysis called restricted mean survival time (RMST), which also adjusts for factors such as disease duration and rate of progression, age, and background ALS therapies, CNM-Au8 was associated with a survival benefit of just over four months. These gains were particularly enhanced in those considered to have moderate or severe ALS, where CNM-Au8 was associated with a nearly one-year median survival gain and a 44% lower risk of death (6.5-month survival gain).
The strongest survival benefits were seen in the subset of patients who met the enrollment criteria for RESTORE-ALS, which generally reflects a population with moderate to severe disease whose symptoms started within the last three years. There, median survival increased from less than two years in Regimen A to nearly three years with CNM-Au8, a difference of nearly 15 months. CNM-Au8 was associated with an RMST improvement of 7.1 months in this population, amounting to a 49% lower risk of death.
The findings are consistent with survival benefits of CNM-Au8 observed in the Phase 2 RESCUE-ALS trial (NCT04098406) and its open-label extension (NCT05299658), as well as in CNM-Au8 expanded access programs.
“The innovative design of the HEALEY ALS platform trial has enabled us to extract clear and meaningful survival data that helps make decisions about CNM-Au8 drug development,” said Merit Cudkowicz, MD, principal investigator and sponsor of HEALEY ALS, and director of the Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital.
In RESTORE-ALS, patients on stable background therapy will receive CNM-Au8 or a placebo for 108 weeks, or just over two years. The main goal is to evaluate CNM-Au8’s ability to extend survival, with a secondary goal of assessing its ability to delay clinical worsening.
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