Clene, FDA to discuss survival data and approval path for CNM-Au8
Company plans to show how the ALS therapy lowers nerve damage markers
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Clene will meet FDA to discuss CNM-Au8, an experimental oral therapy for ALS.
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CNM-Au8 reduces nerve damage markers (NfL), which is linked to improved survival in ALS.
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Clene seeks accelerated approval for CNM-Au8 based on these biomarker data.
Clene is scheduled to meet with the U.S. Food and Drug Administration (FDA) in the coming months to discuss new data and a potential path toward accelerated approval for CNM-Au8, an oral therapy being developed for amyotrophic lateral sclerosis (ALS).
The company plans to argue that the treatment’s ability to lower key markers of nerve damage is directly linked to better survival outcomes for patients.
“ALS remains a devastating disease with limited therapeutic options, and the field urgently needs biomarkers that can meaningfully inform drug development,” Rob Etherington, CEO of Clene, said in a company press release. “We appreciate the FDA’s willingness to engage in a detailed discussion of our biomarker and survival data.”
At the upcoming meeting, Clene hopes to align with the FDA on plans to submit an accelerated approval application for CNM-Au8. Accelerated approval is a type of conditional approval where the FDA allows a treatment to be marketed based on early biomarker data suggesting it’s likely to benefit patients. Developers are then required to conduct additional testing to demonstrate that the therapy actually benefits patients, with future approval contingent upon the results.
Biomarkers and approval
Clene is specifically hoping to file for accelerated approval based on clinical data showing that the therapy can reduce levels of neurofilament light chain (NfL), a marker of nerve damage, and that these reductions are strongly associated with better survival outcomes.
“Our goal in the upcoming Type C meeting is to review the totality of evidence supporting NfL and other emerging biomarkers and to seek FDA guidance on how these data may inform future regulatory pathways for CNM-Au8, including potential accelerated approval,” Etherington said.
The meeting will focus in part on new analyses that Clene completed late last year in response to an FDA request. These findings, which included data from the HEALEY ALS platform trial (NCT04297683) and an expanded access program sponsored by the National Institutes of Health, showed that CNM-Au8 consistently reduced NfL levels.
The analyses also include data from other studies showing that long-term increases in NfL levels are “robustly and consistently” associated with increased mortality risk in ALS patients.
Consistently, the NfL reduction seen in people treated with CNM-Au8 (by about 9%-10%) was associated with an approximately 8%-13% lower risk of death. People with greater NfL reductions experienced proportionately longer survival times.
“Together, these results support the biological and clinical relevance of NfL trajectory as a prognostic biomarker in ALS and provide quantitative context for interpreting NfL changes observed in interventional clinical studies,” Clene stated in the release.
The HEALEY ALS platform trial is an ongoing study that simultaneously tests several experimental ALS therapies. The CNM-Au8 arm of the trial (NCT04414345) aimed to demonstrate that CNM-Au8 (at doses of 30 mg and 60 mg) was superior to a placebo in slowing functional decline.
While the trial missed its main goal, data nonetheless indicated the 30 mg dose of CNM-Au8 reduced the risk of death and delayed clinical worsening, with long-term data from an open-label extension showing a consistent survival benefit.
In its new analyses, Clene also found that CNM-Au8 decreased levels of a cell stress marker, IGFBP7, and that this decline was strongly associated with improved survival among patients.
According to the company, data from other studies have shown that people with mutations that cause low IGFBP7 are more likely to experience a rare phenomenon called ALS reversal, in which the disease stops progressing, and patients improve for unexplained reasons.
“Together, these data suggest that lower IGFBP7, whether achieved genetically or pharmacologically, may help protect against ALS progression,” the company said, noting that “These findings are exploratory and hypothesis-generating and require prospective confirmation.”
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