FDA outlines steps to consider accelerated approval of CNM-Au8
Developer Clene plans to submit application in mid-2025
The U.S. Food and Drug Administration (FDA) signaled that it may be willing to consider granting accelerated approval to CNM-Au8 to treat amyotrophic lateral sclerosis (ALS), based on data from clinical trials and ongoing expanded access programs.
The therapy’s developer, Clene, said it will put together an application in the coming months, with the goal of submitting it in mid-2025.
“We are incredibly grateful for the FDA’s willingness to consider how the available data from our expanded access programs may be able to support the existing clinical study data to allow for the review of an application for approval of CNM-Au8 for ALS via an accelerated regulatory pathway, and for the valuable feedback we have received to date,” Rob Etherington, president and CEO of Clene, said in a company press release.
The accelerated approval process is a tool the FDA can use to facilitate the approval of a promising new treatment based on early clinical data suggesting that is likely to benefit patients. If CNM-Au8 were to be granted accelerated approval, Clene would be required to conduct additional testing to prove whether the therapy actually improves patient outcomes, and continued approval would be conditioned on positive results.
In this case, the FDA said it might consider accelerated approval of CNM-Au8 based on data suggesting that the therapy can lower levels of neurofilament light chain (NfL), a well-established marker of nerve damage.
A dose of caution
The agency cautioned, however, that whether NfL levels can be a reliable marker of CNM-Au8’s clinical benefit in ALS — and whether reductions seen with CNM-Au8 are substantial enough to suggest clinical benefit — will be subject to further review.
The FDA previously said that Clene’s data package for CNM-Au8 wouldn’t be enough to support accelerated approval of the therapy, but the agency reversed course following a meeting with Clene in November, when the company shared additional data and analyses.
Data from early clinical trials, including the Phase 2 study RESCUE-ALS (NCT04098406) and the HEALEY ALS Platform Trial (NCT04297683), suggested that CNM-Au8 can lower NfL levels, and that patients who experience a decrease in NfL levels with CNM-Au8 treatment may experience improved survival compared with those that don’t.
Data from expanded access programs (EAPs), which allowed ALS patients to receive the experimental therapy outside of clinical trials, also have indicated that CNM-Au8 can reduce NfL and improve patient survival, according to Clene.
The company said it putting together a data package addressing the therapy’s effects on NfL and other disease biomarkers in its three EAPs and two clinical trials as part of its planned application for accelerated approval. Clene will meet with the FDA early next year to review and finalize its NfL analyses of EAP data.
“Having seen first-hand the potential benefits of CNM-Au8 in both its clinical and compassionate use EAP programs, I am grateful that the FDA has recognized the power of real-world experience for a drug in ALS, and is willing to consider how EAP data can help ALS drugs advance on regulatory pathways,” said Jinsy Andrews, MD, an investigator on a CNM-Au8 EAP and an associate professor of neurology at Columbia University.
Across clinical trials and EAPs, no serious side effects associated with CNM-Au8 have been reported to date.
“Together with the survival and supportive biomarker data generated thus far, the drug’s benign safety profile, and the emerging EAP NfL data, we look forward to continued discussions with the [FDA],” Etherington said. “Clene plans to include the additional data in an NDA [new drug application] submission under the accelerated approval pathway in mid-2025.”
Clene also plans to launch a Phase 3 trial called RESTORE-ALS, which will be designed with the main goal of definitively proving whether CNM-Au8 can extend survival in people with ALS. A secondary goal is to show that CNM-Au8 can definitely delay clinical worsening events compared with a placebo.
If results from the Phase 3 study are positive, they could potentially serve as confirmatory evidence to convert an accelerated approval into a full traditional approval. Clene said it plans to launch the Phase 3 study next year, and patient enrollment will likely kick off before the company submits the application for accelerated approval.
“We remain dedicated to the ALS community and honored to help critically ill patients and their families,” Etherington said.
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