Clene Receives FDA Roadmap for Potential Accelerated Pathway of CNM-Au8 in ALS

Clene Nanomedicine Inc., a late-stage biopharmaceutical company focused on improving mitochondrial health and protecting neuronal function, has received additional written guidance and a roadmap from the U.S. Food and Drug Administration’s (FDA) Division of Neurology 1 regarding a potential accelerated approval pathway for its lead drug candidate, CNM-Au8, in the treatment of amyotrophic lateral sclerosis (ALS). The company announced this development on September 16, 2024, following an in-person Type C meeting with the FDA on November 1, 2024.

Clene's CNM-Au8 is an oral suspension of gold nanocrystals designed to improve cellular energy production and utilization, which is critical for maintaining neuronal health. The drug candidate has already demonstrated significant improvements in survival rates, functional status, and combined assessment of function and survival in Phase 2 clinical trials. Additionally, over 700 patient years of use of CNM-Au8 have shown no significant safety concerns or safety trends, with no serious adverse events identified as related to CNM-Au8 treatment by any investigator to date.

The FDA's guidance on a potential path to meet the regulatory standard for substantial evidence of effectiveness supporting accelerated approval came following Clene's presentation of additional clinical trial data and analyses during the November 1, 2024 Type C meeting. The FDA recommended that Clene leverage additional Neurofilament Light (NfL) data from its three Expanded Access Programs (EAPs) to support earlier findings.

Clene intends to follow the FDA's recommendation to provide data from the ongoing EAPs and believes that it can address the FDA's requests. The company plans to complete the additional NfL biomarker collection and analyses to support an NDA submission for CNM-Au8 during the second quarter of 2025. The key analyses Clene will conduct include:

1. NfL biomarker analyses: Provide evidence of NfL reductions in participants enrolled in the three FDA-authorized compassionate use EAPs.
2. Survival pharmacometric modeling: Analyze NfL and related disease-specific biomarkers to evaluate their association with clinical survival benefits and observed clinical changes in Phase 2 trial data.
3. ALS-specific biomarker insights: Examine additional ALS-specific biomarkers to further support the pharmacodynamic activity of CNM-Au8 as a treatment for ALS.

Clene will have another meeting with the FDA in early 2025 to review and finalize its statistical analysis plan for the EAP NfL biomarker analyses. The FDA is expected to review whether NfL can serve as a likely surrogate endpoint for the effects of CNM-Au8 in ALS and whether the magnitude of change observed on NfL in patients treated with CNM-Au8 is likely to predict clinical benefit for ALS.

The FDA's guidance was welcomed by Rob Etherington, President and CEO of Clene, who stated, "Together with the survival and supportive biomarker data generated thus far, the drug’s benign safety profile, and the emerging EAP NfL data, we look forward to continued discussions with the Agency. Clene plans to include the additional data in an NDA submission under the accelerated approval pathway in mid-2025. We remain dedicated to the ALS community and honored to help critically ill patients and their families."

Before filing the NDA, Clene intends to begin patient enrollment in a confirmatory Phase 3 RESTORE-ALS trial designed to investigate the effects of CNM-Au8 on improved survival (primary endpoint) and delayed time to ALS clinical worsening events (secondary efficacy endpoint).

Clene's receipt of the FDA roadmap for a potential accelerated approval pathway for CNM-Au8 in ALS is a significant milestone for the company and the ALS community. The additional data and analyses planned by Clene, along with the support of the FDA, could pave the way for a faster approval process and potentially provide a much-needed treatment option for ALS patients.