Clene Eyes Q4 NDA for ALS Drug After FDA-Requested Biomarker Analyses

Key Points

• Clene plans to submit an NDA for CNM-Au8 in ALS at the start of Q4 after completing FDA-requested analyses linking neurofilament light-chain changes to clinical benefits. The FDA indicated the data may support accelerated approval review if that connection is demonstrated.
• Among patients whose neurofilament levels declined or stabilized, Clene reported a 74% lower 12-month mortality risk versus controls, along with statistically significant improvements in ALS functional scores and breathing capacity.
• The company expects an FDA filing decision and potential PDUFA date by year-end, with a possible commercialization decision by early summer 2027; its safety database represents approximately 1,250 patient-years of exposure.

Clene NASDAQ: CLNN is preparing to submit a New Drug Application, or NDA, seeking accelerated approval for CNM-Au8 in amyotrophic lateral sclerosis, or ALS, after completing additional analyses requested by the U.S. Food and Drug Administration, President and CEO Rob Etherington said in an interview.

Etherington said the company met with the FDA in late March and received meeting minutes in early May outlining the agency’s request for more data on neurofilament light chain, a biomarker associated with neurodegeneration. According to Etherington, the FDA said Clene’s data “may be capable of supporting a submission and review” under the accelerated approval pathway, provided the company could demonstrate CNM-Au8’s effect on neurofilament and connect the magnitude of that change to clinical benefit.

Company Cites Survival and Functional Analyses

Clene spent approximately 90 days conducting analyses designed to address those FDA requests, Etherington said. The company reported that survival benefits were concentrated among participants whose neurofilament levels declined or stabilized while receiving CNM-Au8, compared with concurrently randomized controls from the HEALEY ALS Platform Trial.

Etherington said patients in that neurofilament-response group had a 74% lower risk of death after 12 months versus the controls, with a reported P value of 0.01. Across the full follow-up period of up to four years, the company reported a P value of 0.03 for survival.

The company also reported functional findings among patients with declining or stable neurofilament levels. Etherington said the analyses showed statistically significant results for the ALS Functional Rating Scale, or ALSFRS, with a P value of 0.03, and for slow vital capacity, a measure of breathing function, with a P value of 0.003.

“The agency has in their statute that there needs to be a surrogate endpoint change, and we have that,” Etherington said. “They’ve been very clear, there needs to be connection of the neurofilament drop to clinical benefit.”

FDA Focuses on Biomarker-Clinical Benefit Link

Etherington said the FDA acknowledged that neurofilament is prognostic, meaning higher levels are associated with greater mortality risk, but requested evidence of both correlation and causation between biomarker changes and clinical outcomes.

Clene used a randomization-based causal analysis to evaluate whether the observed survival benefit was concentrated in neurofilament responders, he said. The company believes its completed package addresses the agency’s request to show that a reduction in neurofilament is reasonably likely to predict clinical benefit.

While the HEALEY ALS Platform Trial did not meet its primary efficacy endpoint, Etherington said the subsequent analyses indicated that functional and breathing benefits were seen specifically among patients whose neurofilament levels declined or stabilized on treatment.

Neurofilament Results Across Programs

Clene also cited consistency across its clinical programs. Etherington said the company observed an approximately 10% neurofilament reduction in the HEALEY ALS Platform Trial and a similar reduction in an expanded access program sponsored by the National Institutes of Health.

He said the expanded access population included patients who were more severely ill than those in the clinical trial. Clene also used results from its RESCUE-ALS trial as an additional source of evidence, reporting that it observed a comparable reduction in neurofilament in that study.

• Approximately 10% neurofilament reduction in the HEALEY ALS Platform Trial, according to the company.
• Approximately 10% reduction in the NIH-sponsored expanded access program.
• Similar neurofilament findings reported from the RESCUE-ALS trial.

NDA Submission Expected at Start of Fourth Quarter

Etherington said Clene is in the final stages of completing clinical study reports and other elements of its NDA package. The company plans to submit the application at the start of the fourth quarter.

The submission will include data from Clene’s VISIONARY-MS program, although Etherington said the ALS neurofilament and clinical-benefit analyses will be central to the FDA review. He also highlighted the company’s safety database, which he said includes 1,250 collective patient-years of exposure and some patients who have remained on treatment for as long as 6.8 years.

After submission, Clene expects the FDA to determine whether to accept the application and assign a Prescription Drug User Fee Act, or PDUFA, review date. Etherington said the company hopes for that decision by the end of the year if the agency remains on schedule. A potential commercialization decision could follow by early summer 2027, he said.

About Clene (NASDAQ:CLNN)

Clene NASDAQ: CLNN, also known as Clene Nanomedicine, is a clinical-stage biopharmaceutical company developing proprietary nanoparticle therapies aimed at treating neurodegenerative and demyelinating disorders. The company's flagship product, CNM-Au8, is a suspension of catalytic gold nanocrystals designed to enhance cellular energy metabolism, promote remyelination, and reduce oxidative stress. Clene's platform leverages the unique physicochemical properties of its nanoparticles to support neuronal health, with a focus on diseases that currently lack effective disease-modifying treatments.

Clene's lead candidate, CNM-Au8, is undergoing multiple clinical trials targeting conditions such as amyotrophic lateral sclerosis (ALS), Parkinson's disease, and multiple sclerosis (MS).

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