Results from RESCUE-ALS Study Demonstrate Safety and Efficacy of CNM-Au8 for Treatment of ALS

Results from the RESCUE-ALS trial (NCT04098406) and open label extension ([OLE] NCT05299658) demonstrated the safety and tolerability of CNM-Au8 (Clene Nanomedicine, Salt Lake City, UT) as treatment for patients with amyotrophic lateral sclerosis (ALS). CNM-Au8 is a catalytically active, gold nanocrystal agent that exerts antioxidant effects and provides energetic support to the central nervous system by increasing NAD+ and ATP concentrations.

The phase 2, randomized, double-blind, placebo-controlled RESCUE-ALS trial included 45 participants from 2 multidisciplinary ALS clinics in Sydney, Australia with diagnosis of possible, probable, or definite ALS per the Awaji-Shima criteria. Participants were included if they were newly symptomatic within 24 months of screening or within 12 months of diagnosis. During the 36-week trial, participants were randomized 1:1 to receive oral doses of either CNM-Au8 30 mg (n=23) or matched placebo (n=22) once daily. Following this trial, 36 eligible participants entered the OLE and received CNM-Au8 30 mg once daily.

Researchers quantitatively assessed ALS disease progression by decline in motor unit number index (MUNIX), a neurophysiological biomarker. The primary outcome was mean percent change to week 36 of summated MUNIX scores of 4 spinal cord-innervated limb muscles: abductor digit minimi (ADM), abductor pollicis brevis (APB), biceps brachii (BB), and tibialis anterior (TA). Respiratory function was measured as erect forced vital capacity (FVC). No significant differences were observed between the CNM-Au8 and placebo treatment groups for percent change of summated MUNIX score, total MUNIX score change, or FVC change. Survival analyses through 12-month after last-patient last-visit (LPLV) of the double-blind period showed a 60% reduction in all-cause mortality for treatment with CNM-Au8 (hazard ratio = .408 [95% Wald CI: .166-1.001; log-rank P=.0429]). OLE results revealed that participants initially randomized to CNM-Au8 exhibited a slower rate of disease progression. Overall, CNM-Au8 was well-tolerated, and no safety issues were observed.

The study authors note that this is the first ALS clinical trial to use a neurophysiological biomarker as the primary outcome, which helps advances the clinical framework for assessment of ALS treatments.