Clene Inc. announced plans to file a New Drug Application (NDA) with the US FDA for CNM-Au8, an oral suspension of gold nanocrystals, seeking accelerated approval for the treatment of amyotrophic lateral sclerosis (ALS). The filing, which the company said it expects to submit in Q3 2026, follows a Type C meeting with the agency during which the FDA indicated that Clene's proposed dataset "may be capable of supporting the submission and review of an NDA under the accelerated approval pathway for the treatment of ALS".
The planned submission would proceed under Subpart H of the accelerated approval regulations, with CNM-Au8's effect on neurofilament light chain (NfL) — a circulating biomarker of neuronal damage — proposed as a surrogate endpoint reasonably likely to predict clinical benefit. The FDA noted in its meeting minutes that NfL "could potentially serve as a reasonably likely surrogate endpoint" in this context, while also requesting that Clene provide additional data in the NDA to support a connection between the observed magnitude of NfL reduction and clinical benefit. CNM-Au8 holds Orphan Drug Designation for ALS. No PDUFA date has been announced, as the NDA has not yet been submitted.
The NDA package, as described by Clene, will draw on NfL biomarker and clinical data from two Phase II controlled trials and supplementary sources. The HEALEY ALS Platform Trial (NCT04414345), a multi-regimen platform study with a primary completion date of April 2022, evaluated CNM-Au8 against placebo in ALS patients; results published in JAMA (PMID: 40067821) are cited as a core component of the submission. The RESCUE-ALS trial (NCT04098406), a randomized, double-blind, placebo-controlled Phase II study completed in July 2021, provides an earlier controlled dataset with electromyography-based disease progression as its primary endpoint. Supporting data will also come from the open-label extension of the HEALEY platform and an NIH-sponsored expanded access protocol. Clene said the supporting data include reductions in plasma NfL associated with longer survival in the open-label extension period.
The regulatory strategy reflects a broader shift in how the FDA has approached ALS drug development, particularly following the 2023 accelerated approval of Qalsody (tofersen) by Biogen and Ionis Pharmaceuticals, which was also granted on the basis of NfL reduction as a surrogate endpoint. That precedent established NfL as a viable regulatory anchor in ALS, though tofersen's indication is restricted to the approximately 2% of patients carrying SOD1 gene mutations. CNM-Au8, by contrast, is not genotype-restricted, positioning it as a potential option for the broader ALS population if approved.
The current ALS treatment landscape offers limited options. Riluzole, approved in 1995, extends median survival by approximately two to three months. Edaravone, approved in 2017 for a narrowly defined early-stage population, slows functional decline by roughly 33% on the ALSFRS-R scale in that group. Qalsody addresses only SOD1-ALS. Sodium phenylbutyrate/taurursodiol, marketed as Relyvrio, was voluntarily withdrawn from the US market in April 2024 after its Phase III confirmatory trial failed to meet its primary endpoint — a development that narrowed the available armamentarium and underscored the difficulty of translating early ALS signals into confirmatory efficacy.