Clene eyeing regulatory submission for CNM-Au8 in ALS by year’s end
CNM-Au8 is a liquid oral therapy containing gold nanocrystals for nerve cells
Clene Nanomedicine is on track to seek accelerated approval of CNM-Au8 for treating amyotrophic lateral sclerosis (ALS) by the end of the year, backed by neurofilament light chain (NfL) biomarker data from its expanded access program (EAP).
Those analyses, which are intended to address a recommendation from the U.S. Food and Drug Administration (FDA), are due by early fall. The company is preparing to meet with the agency to reach an agreement on the statistical analysis plans for the data in the next couple months.
“We continue to collect NfL biomarker data … in ALS patients, which we still plan to analyze in the third quarter of 2025,” Rob Etherington, president and CEO of Clene, said in a company press release. “Using this data, alongside our data showing CNM-Au8 improved survival over time, we are in active preparations to potentially submit a [new drug application] under the accelerated approval pathway for ALS in the fourth quarter of 2025.” Etherington said the company remains in “active dialogue” with the FDA regarding its submission.
CNM-Au8 is a liquid oral therapy containing gold nanocrystals, which are intended to support the energetic needs of nerve cells, helping them stay healthy and survive.
NfL is an established biomarker of nerve damage that’s associated with ALS progression. Its levels tend to rise as the disease worsens, and reductions in NfL with the experimental treatment are thought to reflect nerve cell protection and slowing disease progression.
Analyzing impact of lower NfL levels
Clene intends to seek accelerated approval of CNM-Au8 for ALS based on clinical trial data showing the therapy lowers NfL levels and that reductions in this biomarker correspond to clinical benefits.
An accelerated approval is a pathway through which the FDA can grant conditional marketing authorization for a therapy based on a surrogate clinical trial endpoint — in this case, reductions in NfL levels — that suggests it will likely lead to functional or survival benefits for patients. Conversion to a traditional approval requires confirmatory studies to establish that benefit.
The FDA previously indicated that NfL biomarker data from two Phase 2 trials wouldn’t be sufficient as a surrogate endpoint, but later reversed course after a meeting with Clene where the company provided additional supportive data. The regulators then indicated they might consider an approval based on NfL data, but recommended additional analyses to support it as a surrogate endpoint.
That supportive data will come from one of the company’s ongoing EAPs, supported by funding from the National Institutes of Health. Also known as compassionate use programs, these studies are intended to enable access to experimental treatments outside traditional clinical trials and can provide information about the real-world benefits of a therapy. Data have so far shown that CNM-Au8 significantly prolonged survival relative to the natural course of the disease.
The planned analyses will look at the treatment’s impacts on NfL levels and compare them to data from a matched group of ALS patients from a large database. They’ll also assess how NfL levels correlate with clinical outcome measures.
Data from other studies, including CNM-Au8’s arm of the HEALEY ALS platform trial (NCT04297683), as well as the Phase 2 RESCUE-ALS trial (NCT04098406) and its open-label extension (NCT05299658), have shown the treatment can prolong survival and slow disease progression.
Clene has also indicated plans to launch the confirmatory Phase 3 RESTORE-ALS trial this year, ahead of the regulatory submission. That study, which could support a full approval, will help establish CNM-Au8’s ability to extend survival and delay disease progression in ALS.
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