CNM-Au8 Shows Prolonged Survival Effect in Amyotrophic Lateral Sclerosis

Kaplan-Meier estimates showed a 61% decreased risk of death on CNM-Au8 compared with predicted median survival from a published European Network to Cure ALS model.

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

For more coverage of MDA 2022, click here.

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