The FDA Rejects Accelerated Approval for Gold Nanocrystal Agent to Treat ALS

The Food and Drug Administration (FDA) has rejected the accelerated approval request for CNM-Au8 (Clene Nanomedicine, Salt Lake City, UT), a catalytically active gold nanocrystal agent developed as a potential treatment for people diagnosed with amyotrophic lateral sclerosis (ALS).

The FDA rejection was based on results from the phase 2 clinical trial program, which did not show evidence of a sufficient reduction of neurofilament light chain (NfL), a biomarker of neurodegeneration.

In September of 2023, Clene Nanomedicine reported results from the phase 2 RESCUE-ALS clinical trial (NCT04098406) and its open-label extension (OLE; NCT05299658) study, which demonstrated a 60% reduction in all-cause mortality for people with ALS treated with CNM-Au8, according to survival analyses through 12 months after last-patient last-visit (LPLV) (hazard ratio [HR] = .408 [95% Wald CI: .166-1.001; log-rank P=.0429]). However, no significant differences were observed at 36 weeks between the CNM-Au8 group and the placebo group in the primary outcome measure of percent change of summated motor unit index (MUNIX), a neurophysiological biomarker. Results reported from the OLE study revealed that participants randomized to receive CNM-Au8 showed a slower rate of disease progression, and that the agent was well-tolerated with no significant safety issues observed.

Clene Nanomedicine has also reported 12-month data from the treatment arm of the ongoing OLE of the phase 2/3 HEALEY ALS platform trial (NCT04297683), a perpetual, multi-regimen clinical trial evaluating the safety and efficacy of CNM-Au8 and other medications as potential treatments for ALS. Participants who received CNM-Au8 showed a 16% decrease in NfL levels compared to placebo at 76 weeks of treatment (95% CI, 2% to 28%; P=.023). Treatment with CNM-Au8 was also associated with a 60% lower risk of long-term all-cause mortality (Cox HR = .40; 95% CI, 0.19 to 0.85; P=.017).

In 2024, Clene Nanomedicine will launch a confirmatory phase 3 study for the use of CNM-Au8 in ALS, and the agent is also being evaluated in late-stage trials for Parkinson disease (PD) and multiple sclerosis (MS). The company states that they intend to provide additional data to the FDA in early 2024.