2023 American Academy of Neurology Abstract Website

James Berry¹, Nicholas Maragakis³, Sabrina Paganoni¹, Melanie Quintana⁴, Eric Macklin⁵, Benjamin Saville⁴, Jinsy Andrews⁶, Jeremy Shefner⁷, Michelle Detry⁴, Parvathi Menon⁸, William Huynh⁹, Colin Mahoney¹⁰, Elijah Stommel¹¹, Meghan Hall⁷, Mariah Connolly⁷, Gale Kittle⁷, Marianne Chase¹, Alexander Sherman¹, Hong Yu¹, Lindsay Pothier¹, Kristin Drake¹, Lori Chibnik², Marie-Abele Bind⁵, Matteo Vestrucci⁴, Robert Glanzman¹², Michael Hotchkin¹³, Steve Vucic¹⁰, Matthew Kiernan¹⁴, Merit Cudkowicz¹, HEALEY ALS Platform Trial Study Group¹⁵, RESCUE-ALS Investigators¹⁶
¹Sean M. Healey and AMG Center for ALS, Massachusetts General Hospital, ²Massachusetts General Hospital, ³Johns Hopkins University School of Medicine, ⁴Berry Consultants, ⁵MGH Biostatistics Center, ⁶Columbia University Medical Center, ⁷Barrow Neurological Institute, ⁸Neurology, Westmead Public Hospital, ⁹Prince of Wales Hospital, ¹⁰University of Sydney, ¹¹Dartmouth-Hitchock Med Ctr/Dept of Neuro, ¹²Clene Nanomedicine Inc, ¹³Clene Nanomedicine, Inc., ¹⁴Brain and Mind Centre, ¹⁵HEALEY ALS Platform Trial, ¹⁶RESCUE-ALS Trial

Objective:

To investigate the efficacy of CNM-Au8 for treatment of ALS.

Background:

CNM-Au8 is a suspension of catalytically active gold nanocrystals shown in models to enhance neuronal metabolic energy. Two trials, RESCUE-ALS and the HEALEY ALS Platform trial (Regimen C) did not show benefit on primary or secondary endpoints. Survival analyses from both studies and an expanded access program (EAP) were investigated.

Design/Methods:

Survival analyses were conducted from the two placebo-controlled trials: (i) long-term follow-up of RESCUE-ALS (Phase 2 randomized, double-blind, placebo-controlled trial (RCT)), and (ii) 24-week HEALEY ALS platform trial (Phase 2/3 perpetual multi-center, RCT). Also presented are data from a single-center EAP compared to ENCALS predicted survival.

Results:

In RESCUE-ALS, while primary analyses did not reach significance over 36-weeks, analyses of all-cause mortality comparing participants originally randomized to CNM-Au8 30mg to those initially randomized to placebo and followed up to 31.5 months demonstrated a significant survival benefit with CNM-Au8 treatment, resulting in >70% decreased risk of death (5 vs. 14 events, log-rank hazard ratio = 0.291; 95% CI: 0.118 to 0.718, p=0.0115).

In the HEALEY-ALS platform trial Regimen C, primary analyses did not show a benefit. Exploratory analysis showed a >90% reduction in risk of death alone or death/permanently assisted ventilation (PAV) at week 24 for the 30mg dose, but not 60mg, when adjusted for baseline imbalances in risk (Regimen C: PAV and death, 4 vs. 1, p=0.028, death only, 3 vs. 1, p=0.057; unadjusted for multiple comparisons).

Survival data from the EAP of CNM-Au8 30mg will be presented.

Conclusions:

Despite the absence of effect on primary and secondary analyses in the RESCUE-ALS and HEALEY ALS Platform trials, the survival results are notable. Exploratory long-term follow-up from RESCUE-ALS and 24-week treatment in the Healey ALS platform trial provide evidence for enhanced survival with CNM-Au8 30mg. EAP data will be presented.