CNM-Au8 Shows Survival Benefit for Patients With ALS in Phase 2 Extension

Interim data from the phase 2 RESCUE-ALS trial open-label extension suggest that Clene Nanomedicine’s investigational agent, CNM-AU8, offered benefits to patients with ALS in terms of survival, in addition to prior results suggestive of slowed progression.

Clene Nanomedicine has announced new interim data from the open-label extension of its phase 2 RESCUE-ALS trial (NCT04098406), which evaluated the investigational oral suspension of gold nanocrystals, known as CNM-AU8, in patients with amyotrophic lateral sclerosis (ALS). The data suggest that those treated with the therapy experienced a 70% survival benefit.1,2

Presented at the 2022 American Academy of Neurology (AAN) Annual Meeting, April 2-7, in Seattle, Washington, by study investigator Matthew Kiernan, MBBS, PhD, DSc, FRACP, FAHMS, the data demonstrated a hazard ratio of 0.3 (P = .006, log-rank test) for those treated with the study drug when compared with the estimated mean survival from the European Network for the Cure of ALS (ENCALS) prediction model.1 In total, the extension included 90% of eligible patients (n = 36) from the base trial.

“Following the 36 weeks of placebo versus active compound, we put everyone on the active compound, and we've been following them up. We did the census of the data in March, and it really is quite dramatic, showing that the survival in patients is improved on nanocrystalline gold, CNM-Au8. And that was the case whether the patients were on the active part in the trial, or indeed on the placebo and then switched to the active part,” Kiernan told NeurologyLive®, adding that importantly, the data show not only an improvement in survival, but a noteworthy improvement in quality of life.

“There's less events for patients, less complications, more survival, and less deaths on the active compound, nanocrystalline gold. Really, this is quite a dramatic finding in ALS patients,” Kiernan, who is Bushell Chair of Neurology and professor of medicine at the Central Clinical School, as well as the codirector of Discovery and Translation at the Brain and Mind Centre of the University of Sydney and a neurologist in the Institute of Clinical Neurosciences at Royal Prince Alfred Hospital, added.

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The trial was a phase 2 multicenter, randomized, double-blind, parallel-group, placebo-controlled trial designed to assess efficacy, safety, pharmacokinetics, and pharmacodynamics of CNM-Au8 in 45 participants with early ALS over 36 weeks of treatment. Among that 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.1-3 That original blinded period revealed significant results, with CNM-Au8 found to be associated with slowed disease progression (P = .0125), a decreased proportion of participants with a 6-point decline in the ALS Functional Rating Scale-Revised (ALSFRS-R; P = .035), and improved quality of life as measured by the ALS Specific Quality of Life (ALSSQOL-SF) questionnaire (P = .018).

CNM-Au8 was well-tolerated with no safety signals identified over 96 weeks of treatment. 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.3

“This approach—nanocrystalline gold—is really a complete frameshift in thinking about neurodegenerative disease,” Kiernan told NeurologyLive®. “The way it works is that it supports energy processes, it restores energy in brain cells in neurons in the brain. It does this through effects by mitochondria, but also it stops the accumulation of TDP43, the protein compound that spreads through the brain causing disability and deficits for patients with ALS. In addition, it seems to have an antioxidant effect through superoxide dismutase.”

“It is a paradigm shift. A lot of this has come through understanding the disease itself. TDP43 and the connections to ALS was a relatively recent discovery in the last decade. Then, there’s been a lot of interest in ALS with the Ice Bucket Challenge and there’s been a lot of support from industry and philanthropy, and that’s driven the science through the roof. As a result, now we have a lot of compounds coming through,” Kiernan added.

Rob Etherington, CEO, Clene Nanomedicine, noted in a statement that the company is looking forward to the HEALEY ALS Platform Trial results, as survival is a prespecified key secondary end point in that trial. “HEALEY participants will also be offered long-term, open-label extension for 52 weeks following the 6-month blinded study duration, allowing for long-term assessment of survival. Our growing body of evidence from the RESCUE-ALS open label extension—and soon from the HEALEY trial—could potentially change the treatment paradigm for people living with the devastating diagnosis of ALS,” Etherington said.1

CNM-Au8 is additional 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.4

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1. Updated Interim Data from Clene Nanomedicine’s RESCUE-ALS Open-Label Extension Study to be Presented in Emerging Science Program at 2022 AAN Annual Meeting. News release. Clene Nanomedicine. April 1, 2022. Accessed April 1, 2022.
2. Kiernan MC. Long-Term Survival of Randomized Participants Enrolled in the Phase 2 RESCUE-ALS Trial of CNM-Au8, A Cellular Energetic Catalyst. Presented at: AAN Annual Meeting; April 2-7, 2022; Abstract 007.
3. 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
4. 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 April 1, 2022.