Clene Moves Toward Accelerated Approval NDA Filing for CNM-Au8 in ALS

According to a new announcement, Clene Nanoscience is preparing to submit a new drug application (NDA) under the FDA’s accelerated approval pathway for its investigational agent CNM-Au8 as a treatment for amyotrophic lateral sclerosis (ALS) following a recent Type C meeting with the agency.1 The submission, expected in the third quarter of 2026, would be supported primarily by neurofilament light (NfL) biomarker data and prior phase 2 clinical studies.

The regulatory discussion is notable because the FDA indicated that the available dataset “may be capable” of supporting NDA review under accelerated approval and acknowledged that NfL could potentially serve as a reasonably likely surrogate endpoint to show benefit in ALS, a progressive neurodegenerative disease with limited disease-modifying treatment options.1

“We are encouraged by the FDA’s careful evaluation of the benefits and risks associated with Clene’s ALS drug candidate, CNM-Au8, including the biomarker data the company provided,” said Rob Etherington, President and CEO of Clene, in a statement. “The filing of an NDA submission represents an important milestone for CNM-Au8 and for the ALS community. We are committed to working with the Agency on this filing and are conducting the Phase 3 confirmatory study for CNM-Au8, which we intend to commence in the first quarter of 2027.”

Regulatory Pathway and Proposed Evidence Package

The planned NDA for CNM-Au8 is intended to proceed under Subpart H accelerated approval regulations, which allow for approval based on surrogate endpoints reasonably likely to predict clinical benefit in serious conditions with unmet medical need. In this case, Clene proposed using changes in plasma NfL as the primary biomarker supporting efficacy.1

According to the company, the FDA stated that the proposed dataset may support submission and review under this pathway, while also requesting additional evidence linking the magnitude of NfL reduction to clinical outcomes in ALS. The agency further noted that NfL may serve as a “reasonably likely surrogate endpoint,” although this designation remains contingent on regulatory review of the full dataset.1

As previously reported by NeurologyLive, the NDA is expected to include data from the Phase 2 HEALEY ALS Platform Trial, the RESCUE-ALS study, and an NIH-supported expanded access program. These datasets reportedly include biomarker changes associated with survival trends in open-label follow-up cohorts, though these findings have not yet been independently peer reviewed in full.2

Previous Clinical Results With CNM-Au8

RESCUE-ALS was a randomized, double-blind, placebo-controlled phase 2 study of patients with early-stage ALS, testing the efficacy and safety of 30 mg CNM-Au8 daily plus background riluzole for 36 weeks. The study’s primary end point, mean percent change in summed motor unit number index (MUNIX), was not met.3

Overall, there was no significance difference between the CNM-Au8 group and placebo on MUNIX score percent change LS mean difference: 7.7%, 95% CI: −11.9 to 27.3%, p = 0.43), total MUNIX score change (18.8, 95% CI: −56.4 to 94.0), or forced vital capacity (FVC) change (LS mean difference: 3.6, 95% CI: −12.4 to 19.7). Despite this, exploratory and longer-term analyses suggested a 60% or so reduction in all-cause mortality at 12 months in the extension (HR, .408 [95% Wald CI: .166-1.001; log-rank P=.0429), and quality of life improvements (ALSQOL-SF).4,5

Within this large-scale platform trial, CNM-Au8, or regimen C, was evaluated over a 24-week period, using change in ALS Functional Rating Scale (ALSFRS-R) as the primary outcome. Published in JAMA, findings showed no significant benefit on ALS disease progression over 24 weeks vs shared placebo on the primary outcome and other clinical measures.6

Since that publication, Clene has presented post-hoc survival analyses pooling data from RESCUE-ALS and HEALEY, suggesting a strengthened survival signal for the medication. Across the full analysis set, patients receiving 30 mg CNM-Au8 showed a median survival of 951 days compared with 753 days in the Regimen A comparator group, a gain of 198 days (6.5 months), alongside a covariate-adjusted restricted mean survival time benefit of 124 days (95% CI, 3–245; P = 0.045). These findings remained robust across multiple sensitivity analyses that incorporated additional covariates—including baseline serum NfL levels, background ALS therapies, and the TRICALS risk score—further supporting the observed survival advantage.6

Interpretation and Regulatory Considerations

The FDA’s willingness to consider NfL as a potential surrogate endpoint reflects a broader regulatory trend toward biomarker-informed accelerated approvals in neurodegenerative disease. However, the strength of this pathway will depend on the robustness of the correlation between biomarker changes and clinically meaningful outcomes such as survival or functional decline.1

READ MORE: RAG-17 Shows Early Safety and Biomarker Improvements in Phase 1 Study of SOD1-ALS

While Clene’s dataset includes multiple phase 2 sources and expanded access data, the absence of a completed, positive phase 3 confirmatory trial remains a key evidentiary gap. As with other accelerated approvals in neurodegenerative diseases, post-marketing confirmatory trials are likely to play a critical role in validating clinical benefit.

CNM-Au8 Mechanism and Development Background

CNM-Au8 is an oral suspension of catalytically active gold nanocrystals designed to support neuronal metabolic function. According to preclinical models, the therapy is hypothesized to enhance mitochondrial activity, increase cellular energy availability, and reduce oxidative stress in neurons.

To date, the agent has received Orphan Drug Designation for ALS from the FDA, reflecting the rarity and unmet need in the disease area. However, it remains investigational and has not received regulatory approval for any indication.

Limitations and Next Steps

Key limitations include reliance on biomarker-driven endpoints rather than definitive functional outcomes, heterogeneity across contributing datasets, and the lack of randomized phase 3 efficacy confirmation at the time of submission. Clene has indicated plans to initiate a Phase 3 confirmatory study in 2027, which will be essential for full regulatory validation if accelerated approval is granted.

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REFERENCES
1. After successful FDA meeting, Clene plans accelerated approval NDA submission for CNM-Au8 in ALS. Clene Nanoscience. News release. May 4, 2026. Accessed May 4, 2026.
https://www.globenewswire.com/news-release/2026/05/04/
2. Clene Reports Third Quarter 2025 Financial Results and Recent Operating Highlights. News release. Clene Nanomedicine. November 13, 2025. Accessed November 14, 2025. https://www.globenewswire.com/news-release/2025/11/13/3187278/0/en/Clene-Reports-Third-Quarter-2025-Financial-Results-and-Recent-Operating-Highlights.html
3. Vucic S, Menon P, Huynh W, et al. Efficacy and safety of CNM-Au8 in amyotrophic lateral sclerosis (RESCUE-ALS study): a phase 2, randomised, double-blind, placebo-controlled trial and open label extension. The Lancet. 2023;60:102036. doi:10.1016/j.eclinm.2023.102036
4. Results from RESCUE-ALS Study Demonstrate Safety and Efficacy of CNM-Au8 for Treatment of ALS. Practical Neurology. September 20, 2023. Accessed November 14, 2025. https://practicalneurology.com/news/results-from-rescue-als-study-demonstrate-safety-and-efficacy-of-cnm-au8-for-treatment-of-als/2470296/
5. Glanzman R, Menon P, Huynh W, et al. RESCUE-ALS Trial Results: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of CNM-Au8 to Slow Disease Progression in ALS. Presented at: MDA Conference. https://www.mdaconference.org/abstract-library/rescue-als-trial-results-a-phase-2-randomized-double-blind-placebo-controlled-study-of-cnm-au8-to-slow-disease-progression-in-als/
6. Berry JD, Maragakis N, Macklin EA, et al. CNM-Au8 in Amyotrophic Lateral Sclerosis The HEALEY ALS Platform Trial. JAMA Neurol. 2025;333;(13):1138-1149.doi:10.1001/jama.2024.27643