FDA unconvinced by Clene’s request for ALS therapy’s accelerated approval tag

Clene is continuing to struggle to get anyone else to understand what it sees in CNM-Au8, with the FDA unwilling to grant an accelerated approval tag to treat amyotrophic lateral sclerosis (ALS) therapy.

The Salt Lake City-based biotech arrived at a meeting with the agency armed with clinical, biomarker and long-term survival data from phase 2 studies of the oral therapy, a gold nanocrystal suspension. But the FDA was unconvinced that the initial findings showing a reduction in neurofilament light chain (NfL) biomarker were enough to justify an accelerated approval tag, according to Clene.

Undeterred, the company said it plans to show how CNM-Au8’s mechanism of action is linked to the reduction in NfL—a biomarker of nerve injury and neurodegeneration—as well as increased survival time.

“Clene is looking forward to providing supplemental data for further engagement with the FDA in the first half of 2024, including additional long-term clinical evidence and biomarker results of CNM-Au8’s treatment benefit in people living with ALS,” the biotech explained.

The company is still set on launching its confirmatory study of the therapy in ALS next year, it said. For now, CNM-Au8 is available to certain U.S. patients via two compassionate use programs, with a third due to launch soon thanks to $45 million of National Institutes of Health funding, Clene CEO Rob Etherington pointed out in the release.

“As we continue to analyze the data from our phase 2 clinical program, we believe the evidence supports that CNM-Au8 treatment improved survival in people living with ALS,” Clene’s Head of Medical Benjamin Greenberg, M.D., said. “We are also encouraged that the recently disclosed long-term NfL biomarker decreases are consistent with delayed clinical time-to-event outcomes.”

Back in June, Clene pointed to what it claimed was a “statistically significant” reduction in NfL compared to placebo after 24 weeks of treatment. The data came from the HEALEY ALS Platform Trial, which is testing multiple ALS therapies, including a cohort of 161 participants taking CNM-Au8 or placebo.

At the time, the company pointed out that “surrogate biomarkers such as NfL have recently been used to support an FDA approval for the treatment of ALS”—a reference to Biogen’s success in securing accelerated approval for Qalsody in April to treat a subset of ALS patients off the back of a reduction in NfL.

By August, Clene was highlighting a fresh slice of long-term data from the phase 2 RESCUE-ALS trial of CNM-Au8 in ALS. While the initial readout in 2021 showed that the study missed its primary endpoint, Clene continued collecting data in an open-label extension and has since reported that patients who received CNM-Au8 were living longer.  

Clene’s open-label updates have all failed to convince investors to overlook its earlier setbacks. In addition to the failure of the original RESCUE-ALS analysis, the biotech reported a missed primary endpoint in a second midphase trial of CNM-Au8 late last year.

The biotech’s share price slumped further in pre-market trading this morning, dropping 24% to 38 cents per share from a Wednesday closing price of 51 cents.