CNM-Au8 Shows Efficacy Signals for ALS Despite Failing to Reach Primary End Point


Through 36 weeks of treatment with CNM-Au8, investigators observed a slowing of disease progression and decreased number of participants with a 6-point decline on ALSFRS-R.

Matthew Kiernan, PhD, DSc, FRACP, FAHMS

Matthew Kiernan, PhD, DSc, FRACP, FAHMS

Newly announced topline results from RESCUE-ALS (NCT04098406), a phase 2 clinical trial evaluating CNM-Au8 (Clene Nanomedicine) in patients with amyotrophic lateral sclerosis (ALS), showed that the investigational agent 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.

Clene noted that it plans to present topline results from the study at the upcoming International Symposium on ALS/MND, which will take place December 8-10, 2021. Clene is also expected to report results from the HEALEY ALS Platform Trial, which involves several different investigational agents, including CNM-Au8, in the second half of 2022.

RESCUE-ALS, a 36-week, placebo-controlled trial, included 45 patients with ALS who were randomized 1:1 to either 30-mg daily CNM-Au8 or matching placebo on top of standard of care. As a catalytically active gold nanotherapeutic that drives cellular energy, CNM-Au8 represents a unique approach to ALS care. The agent is designed to produce reactions in the brain that enable neuroprotection and remyelination through increasing neuronal and glial resilience to disease-relevant stressors.

Change in MUNIX, a neurophysiological biomarker that estimates the number of functioning lower motor neurons serving selected muscles, was found to be nonsignificant at the end of the treatment period; however, investigators noted an efficacy signal observed at week 12 (P = .057). In a subset of patients with limb onset ALS, which accounts for approximately 70% of the ALS population, CNM-Au8 showed a significant treatment effect in MUNIX at week 12 (P = .057), with a trend for improvement at week 36 (P = .0741).

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At week 36, CNM-Au8-treated patients demonstrated significant benefits in several exploratory end points, including slowing ALS disease progression (P = .0125), decreasing the proportion of participants with an ALS Functional Rating-Scale Revised 6-point decline (P = .035), an improving quality of life as measured by the ALS Specific Quality of Life (P = .018).

"These data are very encouraging to us in the ALS research and treatment community as they demonstrate clinical benefits with CNM-Au8 treatment in outcomes that matter to patients and provide evidence for improved long-term survival,” trial investigator Matthew Kiernan, PhD, DSc, FRACP, FAHMS, chair of neurology, University of Sydney, said in a statement.1 "RESCUE-ALS was a proof-of-concept trial intended to establish that treatment of neuronal energetic failure can provide disease-modifying effects in ALS. I am pleased to see the potential effectiveness of CNM-Au8 demonstrated in this trial, and it is important to confirm these results in a larger clinical trial."

The oral treatment was found to be well tolerated in RESCUE-ALS, with no serious adverse events (SAEs) related to study drug occurring. Aspiration pneumonia (n = 3) and transient gastrointestinal distress (n = 2) were among the most frequently reported AEs associated with CNM-Au8 treatment.

"The results of RESCUE-ALS add to our expanding body of evidence that cellular energetic failure is an important pathophysiological mechanism in ALS," Robert Glanzman, MD, FAAN, chief medical officer, Clene, said in a statement.1 "We thank the trial participants and their families for their willingness to engage in clinical research, the site investigators for their research excellence and dedication to patients, and FightMND of Australia for substantially funding the trial."

This news comes on the heels of a September 2021 announcement from Clene that it had launched its second FDA expanded access program (CNMAu8.EAP02) with CNM-Au8 for patients with ALS. This was launched in conjunction with the Healey ALS Platform Trial, after the first expanded access program (CNMAu8.EAP01), also launched in partnership with the Healey & AMG Center. The first program supports access to the investigational agent for 40 people living with ALS, with enrollment beginning in September 2019 and long-term participants now treated for over 100 weeks.2

CNM-Au8 is currently also being evaluated for several other neurological disorders, including multiple sclerosis (MS) and Parkinson disease (PD). The phase 2 REPAIR clinical trials showed that the treatment can significantly improve brain energetic metabolism in both of these patient groups. REPAIR, which includes REPAIR-MS (NCT03993171) and REPAIR-PD (NCT03815916), resulted in statistically significant increases by an average of 0.589 units (10.4%) in the mean change in the brain ratio of oxidized nicotinamide adenine dinucleotide to reduced nicotinamide adenine dinucleotide after 12 weeks of treatment.3

1. Clene Nanomedicine announces top-line results from phase 2 RESCUE-ALS clinical trial. News release. November 2, 2021. Accessed November 2, 2021.
2. Clene announces initiation of a second FDA expanded access program with CNM-Au8 for people living with amyotrophic lateral sclerosis. News release. Clene Nanomedicine. September 23, 2021. Accessed November 2, 2021.
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 November 2, 2021.
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