CNM-Au8 Did Not Slow ALS Progression in HEALEY ALS Platform Trial

Key Takeaways

• CNM-Au8 did not slow ALS disease progression compared with placebo over 24 weeks in the HEALEY ALS Platform Trial.
• Secondary outcomes—Combined Assessment of Function and Survival score, slow vital capacity decline, and survival free of permanent assisted ventilation—likewise suggested no significant difference between placebo groups.
• The findings do not support a clinically meaningful benefit of CNM-Au8—an oral suspension of catalytically active gold nanocrystals—for ALS at the doses studied.

CNM-Au8, an oral suspension of catalytically active gold nanocrystals intended to support cellular energetics by increasing nicotinamide adenine dinucleotide (NAD+) and adenosine triphosphate (ATP) production, did not meaningfully alter amyotrophic lateral sclerosis (ALS) progression over 24 weeks in participants in the HEALEY ALS Platform Trial (NCT04414345). The findings do not support a clinically meaningful effect for CNM-Au8 on ALS progression.

The phase 2/3, multicenter, randomized, double-blind platform trial was conducted at 54 US sites from July 2020 to March 2022. A total of 161 participants with ALS were randomized 3:3:2 to CNM-Au8 60 mg daily (n=61), CNM-Au8 30 mg daily (n=59), or matched placebo (n=41) for 24 weeks. Analyses incorporated an additional 123 concurrently randomized shared placebo participants from other platform regimens. The primary outcome used a Bayesian shared-parameter model combining function (via the Revised ALS Functional Rating Scale [ALSFRS-R]) and survival to estimate a disease rate ratio (DRR; <1 indicating benefit). Secondary outcomes included a joint-rank Combined Assessment of Function and Survival (CAFS), slow vital capacity decline, and survival free of permanent assisted ventilation.

Key demographics and findings include:

• Mean age of participants was 58.4 years; 37.9% were female; 90% completed follow-up.
• The primary outcome showed no significant benefit (DRR, 0.97; 95% CI, .783 to 1.175; posterior probability DRR <1=0.65).
• Secondary outcomes likewise suggested no benefit or harm compared with placebo.
• Common adverse events (CNM-Au8 vs placebo) included diarrhea (19% vs 7%) and nausea (14.2% vs 8.6%). Fatigue (10.8% vs 18.4%) and muscular weakness (20% vs 27.6%) occurred more often with placebo.

Source: Writing Committee for the HEALEY ALS Platform Trial, HEALEY ALS Platform Trial Study Group. CNM-Au8 in Amyotrophic Lateral Sclerosis: The HEALEY ALS Platform Trial. JAMA. 2025;333(13):1138–1149. doi:10.1001/jama.2024.27643