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FDA Declines Accelerated Approval for Novel ALS Drug
The US Food and Drug Administration (FDA) declined to grant accelerated approval of the experimental drug CNM-Au8 for the treatment of amyotrophic lateral sclerosis (ALS). The news was announced by the drug manufacturer Clene Nanomedicine, in absence of an official statement from the FDA regarding the rejection.
According to the Clene press release, the FDA “determined that the initial findings on biomarker NfL [(neurofilament light chain)] reduction from the Phase 2 programs were insufficient to support accelerated approval at this time.”
CNM-Au8, “a catalytically active gold nanotherapeutic” that can cross the blood-brain barrier— but is not toxic unlike other synthetic gold compounds—aims to promote remyelination in patients with ALS by targeting brain cell energy production. It is also under investigation for use in patients with multiple sclerosis and Parkinson disease.
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While basic research has demonstrated that the drug “stabilizes mitochondria and reduces accumulation of the TDP-43 protein, which is linked to the spread of ALS through the brain,” CNM-Au8 notably failed to meet the primary endpoint in its Phase 2 trial, defined as the change in the summated motor unit index (MUNIX) from baseline to week 36.
Despite missing the primary endpoint, both Clene and neurologists who presented and commented on the findings at the 2022 American Academy of Neurology Annual Meeting indicated that CNM-Au8 still had therapeutic potential due to its positive safety profile (there were no dropouts from those receiving the active compound during the trial), and significant efficacy as demonstrated by MUNIX at week 12 (p=0.0385) in “protection of lower motor neurons.”
These silver linings, though, proved insufficient to persuade the FDA in Clene’s favor.
On the same day as the rejection announcement, Clene reported results from a Phase 3 open-label extension of the treatment arm in the HEALEY ALS Platform Trial (NCT04297683). Investigators noted a 16% decrease in plasma NfL compared to placebo at week 76 (p=0.023). The treatment group also had a 60% lower risk for long-term mortality. These results have not yet been peer-reviewed.
“We anticipate launching the Phase 3 ALS confirmatory study in 2024,” said Clene CEO Rob Etherington. “Importantly, we also plan to submit new information to the FDA for further discussions on the totality of evidence in order to advance the accelerated development of CNM-Au8 for the treatment of ALS.”
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