CNM-Au8 Shows Prolonged Survival Effect in Amyotrophic Lateral Sclerosis

Robert Glanzman, MD, FAAN

New findings from the open-label extension (OLE) of the phase 2 RESCUE-ALS study (NCT04098406) showed that CNM-Au8 (Clene Nanomedicine) improved survival in patients with sporadic amyotrophic lateral sclerosis (ALS) over a 36-week period compared with the estimated median survival derived from a European Network to Cure ALS (ENCALS) prediction model.¹

These findings, presented at the 2022 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference, March 13-16, in Nashville, Tennessee, build upon topline data announced in November 2021. In the original double-blinded portion, CNM-Au8, an investigational suspension of clean-surfaced, catalytically active gold nanocrystals, did not meet its primary or secondary end points in change of Motor Unit Number Index (MUNIX) biomarker and forced vital capacity (FVC), but did show a MUNIX efficacy signal after 12 weeks of treatment.²

Led by Robert Glanzman, MD, FAAN, chief medical officer, Clene Nanomedicine, participants were randomized 1:1 in the double-blind portion of RESCUE-ALS to either 30-mg CNM-Au8 or placebo daily on top of standard care for 36 weeks followed by an OLE to evaluate long-term efficacy and safety. Among a cohort of 45 participants (CNM-Au8: n = 23; matched placebo: n = 22), 96% of patients who received study drug completed the 36-week observation period.¹

At the end of the 36-week period, there was 1 (4%) recorded mortality event in the active-treatment arm and 2 in the placebo-treated group. In total, 86% of those on placebo completed the study period, with the remaining 14% attributable to death or withdrawal due to disease worsening (n = 1). Of the participants who completed the double-blind portion, 1 subject on CNM-Au8 was ineligible for the OLE due to relocation from Australia, and 4 elected not to continue in the OLE (1 active, 3 placebo), resulting in 90% of eligible participants in the OLE.

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From randomization to the latest OLE observation, long-term survival was calculated and compared to predicted median survival derived from the published ENCALS model which was based on each participant’s baseline study characteristics. Using Kaplan-Meier analyses, investigators identified a significant survival benefit among those treated with CNM-Au8, with a 61% decreased risk of death compared to predicted (log-rank HR, 0.39; 95% CI, 0.17-0.89; P = .026).

The oral treatment showed a safety profile that was consistent with what had been previously observed. In the double-blind portion, there were no serious adverse events (SAEs) related to study drug, and the most frequently reported AEs were pneumonia (n = 3) and transient gastrointestinal distress (n = 2).

In the original dataset, CNM-Au8 demonstrated significant benefits in several exploratory end points, including slowing ALS disease progression (P = .0125), decreasing the proportion of patients with ALS Functional Rating-Scale Revised 6-Point decline (P = .035), and improving quality of life as measured by the ALS Specific Quality of Life (P = .018).²

CNM-Au8 is currently being evaluated in other conditions such as multiple sclerosis (MS) in the REPAIR-MS study (NCT03993171) and Parkinson disease (PD) in the REPAIR-PD trial (NCT03815916). These 2 sequential group studies examine the brain metabolic effects, safety, pharmacokinetics, and pharmacodynamics of CNM-Au8 in patients who have been diagnosed with MS within 15 years of screening or in patients with PD who have been diagnosed within 3 years of screening. In August 2021, the company announced positive topline results from the trials, which showed that the investigational agent significantly improved brain energetic metabolism in both patient groups.³

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REFERENCES
1. Glanzman R, Menon P, Huynh W, et al. Evidence for a potential survival benefit in ALS with CNM-Au8 treatment: results from the RESCUE-ALS trial long-term open-label extension. Presented at: MDA 2022; March 13-16; Nashville, Tennessee. Poster 35

2. Clene Nanomedicine announces top-line results from phase 2 RESCUE-ALS clinical trial. News release. November 2, 2021. https://invest.clene.com/events-and-presentations/Press-Releases/news-details/2021/Clene-Nanomedicine-Announces-Top-Line-Results-from-Phase-2-RESCUE-ALS-Clinical-Trial/default.aspx

3. Clene reports positive top-line results from its phase 2 REPAIR clinical trials in Parkinson disease and multiple sclerosis. News release. August 5, 2021. Accessed August 5, 2021. https://www.globenewswire.com/news-release/2021/08/05/2275392/0/en/Clene-Reports-Positive-Top-line-Results-from-its-Phase-2-REPAIR-Clinical-Trials-in-Parkinson-s-Disease-and-Multiple-Sclerosis.html