Clene submits new CNM-Au8 data to FDA ahead of upcoming meeting
Company, agency to discuss accelerated approval pathway for ALS therapy
Clene will soon meet with the U.S. Food and Drug Administration (FDA) to discuss the potential pathway to accelerated approval for CNM-Au8, the company’s experimental therapy for amyotrophic lateral sclerosis (ALS).
Ahead of the meeting, the company has submitted new data to the agency, including the findings from analyses of two Phase 2 clinical trials — which suggest treatment with CNM-Au8 helps prolong survival in people with ALS, according to the developer.
“The risk-benefit assessment evidence of CNM-Au8 is strong. Our next step is discussing this new CNM-Au8 biomarker and efficacy data with the FDA, with the hope that ALS patients will benefit from this drug, sooner rather than later,” Rob Etherington, president and CEO of Clene, said in a company press release.
The accelerated approval pathway is a mechanism that allows the FDA to authorize a new treatment based on early clinical data suggesting the therapy is likely effective, with the condition that the developer conduct additional testing to prove its benefit.
CNM-Au8 is a gold nanoparticle suspension that’s designed to boost energy generation in cells. Nerve cells require a lot of energy to function, and problems with energy generation are thought to play a role in the progression of ALS and other neurological diseases.
Clene is hoping to secure accelerated approval of CNM-Au8 based on clinical data showing the therapy can reduce levels of neurofilament light chain (NfL), a nerve damage marker that’s associated with ALS progression and mortality risk.
Clene submitted new data showing CNM-Au8’s clinical effectiveness
The new data submitted to the FDA include findings from the HEALEY ALS Platform Trial (NCT04297683), a large study that’s testing multiple potential ALS treatments simultaneously. In this study, participants were randomly assigned to receive daily oral CNM-Au8 or a placebo for 36 weeks, or about eight months, and were then moved to an open-label extension phase in which all are receiving CNM-Au8.
Roughly half of the patients given CNM-Au8 in the trial were deemed NfL responders, meaning they showed notable decreases in NfL levels. In this group, NfL levels were reduced by an average of 28% after about 1.5 years of treatment.
Prior analyses from HEALEY ALS had indicated that CNM-Au8 may extend survival, but the new analyses get more granular with respect to NfL levels. The findings suggest that the risk of death was reduced by approximately 65% in NfL responders compared with patients who did not experience decreased NfL levels with CNM-Au8.
The NfL responders also showed less progression in the ALS Functional Rating Scale-Revised (ALSFRS-R) — which measures the ability to do daily tasks — than non-responders. The responder group similarly declined less in ALSFRS-R measurements of breathing ability; breathing problems are a major driver of mortality in ALS.
Significant differences in a combined assessment of function and survival between the groups were seen as early as about one year after the start of treatment and remained significant out to about two years.
The strong safety profile of CNM-Au8, with its NfL biomarker response now linked to survival evidence, and new information on mechanisms of action support proceeding to a confirmatory Phase 3 clinical trial and regulatory discussions on approval pathways.
In other analyses, Clene researchers compared survival data from ALS patients given CNM-Au8 in HEALEY ALS or the company-sponsored study RESCUE-ALS (NCT04098406) against outcomes from untreated patients in three external datasets: the PRO-ACT database, the ALS/MND Natural History Consortium (NHC), and the Australian MiNDAUS registry.
Results from these analyses consistently indicated that CNM-Au8 treatment reduced the risk of mortality, by anywhere from 48% to 70% depending on the specific studies/registries being used for comparisons.
Additional data from these studies have shown that patients who show signs of improved energy production in nerve cells tend also to experience decreased levels of NfL, supporting the idea that CNM-Au8’s ability to boost energy production may help lessen nerve death in ALS.
“The strong safety profile of CNM-Au8, with its NfL biomarker response now linked to survival evidence, and new information on mechanisms of action support proceeding to a confirmatory Phase 3 clinical trial and regulatory discussions on approval pathways,” said Merit Cudkowicz, MD, principal investigator of the HEALEY ALS trial at Massachusetts General Hospital.
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