Clene Submits New CNM-Au8® Data to FDA for ALS Treatment

Clene Inc., a biopharmaceutical company, has announced promising new data on CNM-Au8, a treatment for amyotrophic lateral sclerosis (ALS). This data, submitted to the U.S. Food and Drug Administration (FDA), includes post hoc analyses from two Phase 2 clinical trials and aims to guide discussions on accelerated approval.

Neurofilament light (NfL) in plasma is a key biomarker for ALS progression and mortality risk. Participants treated with CNM-Au8 who showed sustained reductions in NfL levels, termed "NfL Responders," displayed a 28% mean reduction in NfL levels compared to baseline. In contrast, NfL levels increased in non-responders. The geometric mean ratio difference at week 76 post-baseline stood at 0.57, with a 95% confidence interval (CI) between 0.50 and 0.64, and a highly significant p-value of less than 0.00001.

The data revealed that CNM-Au8 NfL Responders had notable improvements in survival, functional status, and combined function and survival (CAFS scores). Specifically, NfL Responders had significantly improved survival rates compared to propensity-matched controls from the PRO-ACT database, with a hazard ratio (HR) of 0.504 and a 95% Wald CI between 0.28 and 0.904. Also, they exhibited better survival outcomes compared to non-responders, with an HR of 0.350 and a 95% CI between 0.188 and 0.649.

Functional improvements were measured using the ALS Functional Rating Scale-Revised (ALSFRS-R), which evaluates the functional status of ALS patients over time. CNM-Au8 NfL Responders showed significantly less decline in ALSFRS-R scores compared to non-responders, particularly at the 64, 76, 88, and 100-week visits post-randomization. These differences were statistically significant with a p-value of less than 0.01. Additionally, improvements were observed in the respiratory subdomain of the ALSFRS-R for NfL Responders at the same time points.

Combined Assessment of Function and Survival (CAFS) scores also improved for CNM-Au8 NfL Responders, showing significant improvements starting at Week 48 and reaching statistical significance by Week 88.

Independent of NfL responder status, participants treated long-term with CNM-Au8 30 mg showed a significant survival benefit. This was observed in both the RESCUE-ALS and HEALEY ALS Platform Trials when compared to matched natural history controls. For instance, long-term treatment in the HEALEY ALS Platform Trial correlated with a 57% decreased risk of all-cause mortality compared to PRO-ACT matched controls, with an HR of 0.431 and a 95% CI between 0.276 and 0.672.

CNM-Au8 also demonstrated a dual mechanism of action by improving levels of nicotinamide adenine dinucleotide (NAD) and glutathione in patients. This was consistent with the findings in CNM-Au8 NfL Responders, indicating target engagement and suggesting a link between the drug’s mechanism and NfL declines. Biomarkers of oxidative stress, such as the GSH/GSSG ratio, showed consistent improvement with CNM-Au8 treatment, supporting its dual action of metabolic support and reduced oxidative stress.

Merit Cudkowicz, M.D., Chair of the Neurology Department at Massachusetts General Hospital and Principal Investigator of the HEALEY ALS Platform Trial, emphasized the strong safety profile of CNM-Au8 and its link to survival benefits. This supports the move towards a confirmatory Phase 3 clinical trial and subsequent regulatory discussions.

The safety profile of CNM-Au8 remains robust, with over 650 patient-years of data showing no significant safety issues or trends. No serious adverse events related to CNM-Au8 have been identified by investigators so far.

Rob Etherington, CEO and President of Clene, expressed optimism about the strong risk-benefit assessment of CNM-Au8 and plans to discuss the new data with the FDA, hoping to benefit ALS patients sooner.

Overall, Clene continues its mission to improve mitochondrial health and protect neuronal function, focusing on treatments for neurodegenerative diseases like ALS. CNM-Au8, their investigational therapy, shows promise in improving neurological outcomes through its unique mechanism of action.