CNM-Au8 Improves MUNIX(4) Score in Amyotrophic Lateral Sclerosis

Steve Vucic, MBBS, FRACP, PhD, DSc

Clene Nanomedicine recently announced results from its phase 2 interim multi-center, randomized, double-blind, parallel-group, placebo-controlled trial, dubbed RESCUE-ALS (NCT04098406), investigating CNM-Au8 for the treatment of amyotrophic lateral sclerosis (ALS) at the Virtual 31st International Symposium on ALS/MND, December 9–11, 2020.

The data presented showed that over 40% of the 43 participants experienced improvements in motor neuron function as assessed by the motor neuron number index-4 (MUNIX[4]) score. The average MUNIX(4) score increased from baseline for both the CNM-Au8 and placebo groups. This increase in MUNIX(4) exceeded statistic modeling that predicted a linear decline in average (MUNIX-4) score from study onset.¹

These data were presented by Steve Vucic, MBBS, FRACP, PhD, DSc, neurologist, Westmead Hospital, and researcher, University of Sydney, who wrote that “a successful outcome of this study establishes the direct treatment of cellular bioenergetic failure as a therapeutic target for ALS and supports the validation of using electromyography endpoints as biomarkers for ALS disease progression.”²

The 43 participants enrolled in the study had a mean MUNIX(4) score of 92 (standard deviation [SD], 47.3), a forced vital capacity (FVC) average of 80.5 (SD, 16.4), a revised amyotrophic lateral sclerosis functional rating scale (ALSFRS-R) score of 38.5 (SD, 6.1) and an ALS-Specific Quality of Life Questionnaire (ALSSQOL-20) score of 3.3 (SD, 1.3) at baseline. The mean time from diagnosis for the patients was 4.8 months (SD, 4.6), and 86% (n = 37) were being treated with riluzole. The patients were randomized to receive 30 mg of CNM-Au8 once daily or matching placebo over a 36-week double-blind treatment period.

NeurologyLive previously talked to Robert Glanzman, MD, FAAN, Chief Medical Officer, Clene, another investigator on the RESCUE-ALS trial, about CNM-Au8 and its demonstrated potential to reduce neurodegeneration in animal models of diseases like ALS and multiple sclerosis (MS).

Additionally, data presented by Glanzman at the 2020 America’s Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum, February 27-29, 2020, in West Palm Beach, Florida, which included the first 34 participants with MS and chronic optic neuropathy treated with CNM-Au8, showed that they experienced gains in best-corrected low contrast letter acuity (BC-LCLA). Those interim data were from the phase 2 VISIONARY-MS study (NCT03536559).³

CNM-Au8 is a unique suspension of gold nanocrystals absorbed in the blood stream and dispersed throughout the organ system, and no other approved therapies for the treatment of MS have been shown to remyelinate chronic MS lesions. Similarly, no therapies have been shown to slow disease progression across MS, Parkinson disease (PD), nor ALS.

“This blinded interim analysis suggests that CNM-Au8 is working mechanistically to address a foundational challenge common to many neurodegenerative diseases, namely that stressed or failing neurons need additional energy for their survival, repair, and improved function,” Rob Etherington, president and CEO, Clene, commented on the study in a statement. “Emerging MUNIX data potentially indicate preservation of motor units, which is promising. We eagerly anticipate final results and are encouraged that these blinded interim results may provide hope for ALS patients and their families as they search for new therapies to treat this devastating disease.”

REFERENCES

1. Clene Nanomedicine Presents Blinded Interim Results from RESCUE-ALS Phase 2 Study at the 31st International Symposium on ALS/MND. News release. Clene Nanomedicine. December 10, 2020. Accessed December 14, 2020.
2. Vucic S, Glanzman R, Kiernan M, et al. CLT-23: RESCUE-ALS Trial, A phase 2, randomized, double-blind, placebo-controlled study of CNM-Au8 to slow disease progression in amyotrophic lateral sclerosis patients: Design and interim blinded results. Presented at the 31st International Symposium on ALS/MND, December 9-11, 2020. Abstract CLT-23.
3. Beadnall H, Hotchkin MT, Klistorner A, et al. VISIONARY-MS: A Phase 2 Clinical Trial Of Catalytic Gold Nanocrystals, CNM-Au8, For The Treatment Of Chronic Optic Neuropathy. Presented at 2020 ACTRIMS Forum. February 27-29, 2020; West Palm Beach, FL. Abstract P079.