An ALS drug aimed at mitochondria heads toward FDA review

Amyotrophic lateral sclerosis moves fast — most patients die within two to four years of diagnosis — and the medicine cabinet for it is nearly empty. That is why a regulatory milestone matters even before any approval: Clene (NASDAQ: CLNN) says it will submit a new drug application to the FDA at the start of the fourth quarter for CNM-Au8, its investigational ALS treatment, and expects a possible FDA decision around the middle of 2027. The candidate is unusual — an oral suspension of gold nanocrystals intended to support mitochondrial function and neuronal resilience — and its road to filing ran through a trial that missed its primary endpoint.

What is CNM-Au8, and why mitochondria?

CNM-Au8 is not a conventional small-molecule drug or a biologic. CEO Rob Etherington, speaking at the Lytham Partners Fall 2026 Investor Conference, described it as a proprietary oral gold nanocrystal suspension — an intersection, in his words, of physics, materials science and biology. The idea is to support cellular energy production in nerve cells: ALS destroys motor neurons, and failing mitochondria are one of the most consistently documented features of the disease, so a therapy aimed at mitochondrial function is aimed at a plausible root of neuronal decline.

Clene is studying the same candidate in multiple sclerosis and Parkinson's disease. Hundreds of patients are already receiving it through four expanded-access (compassionate use) protocols, which the company says gives it extensive long-term safety data.

What did the trials actually show?

The honest version includes the miss. In the HEALEY ALS platform trial, CNM-Au8 did not meet its primary endpoint on the ALS Functional Rating Scale (ALSFRS), which tracks movement, speech, eating and breathing. Etherington acknowledged that directly. The company's filing case rests instead on other signals: a survival benefit at the 30-milligram dose, a statistically significant benefit on clinical worsening, and improvement on a combined function-and-survival measure called CAFS.

The biomarker story centers on neurofilament light, a blood marker of nerve injury. Clene says it was the only one of eight regimens tested in the HEALEY program to show a nominally significant neurofilament light change in a double-blind, placebo-controlled study — "nominal" because the primary endpoint was missed. The FDA has asked the company to demonstrate that neurofilament reductions are connected to survival, and Clene says it has compiled analyses linking neurofilament trajectories to mortality risk across independent studies. It has held five meetings with the agency over two years and is pursuing a potential accelerated-approval pathway with a confirmatory Phase III survival study to follow.

What happens next — and what this doesn't prove yet

The FDA first decides whether to accept the application for review — Clene expects that call by the end of the year — and only then begins the review that could end in a mid-2027 decision. Acceptance is not approval, and accelerated approval, if granted, would still require the confirmatory survival trial.

For readers, the takeaway is measured: a mitochondria-targeted approach to ALS is reaching the regulatory stage, which is genuinely newsworthy for a disease with few options. But the evidence remains preliminary — built on post-hoc analyses and biomarker arguments after a missed primary endpoint — and CNM-Au8 is not an approved therapy. The company says it recently completed a financing round with enough cash to reach the FDA's acceptance decision.

Where the evidence stands

• Established: ALS is rapidly fatal (typically 2–4 years) with few treatment options; mitochondrial dysfunction is a well-documented feature of motor-neuron decline.
• Preliminary: CNM-Au8's survival and biomarker signals come from analyses after a missed primary endpoint; the FDA has not yet accepted the application for review.
• Absent: No approval exists; whether neurofilament changes predict survival benefit in ALS is still an open regulatory question.