Clene Inc.

About These Analyses

The HEALEY and RESCUE-ALS biomarker analyses described in this release arepost hoc and exploratory; neither trial met its prespecified primary efficacy endpoint, no adjustment was made for multiple comparisons, and reported p-values are nominal. The HEALEY analyses are based on 57 CNM-Au8 30 mg treated participants with an evaluable NfL trajectory (38 NfL Decline/Stable, 19 NfL Increase); the RESCUE-ALS analyses on 22 participants (11 per group). Each NfL stratum was compared with concurrently randomized controls rather than with the other stratum; with 38 and 19 participants respectively, these analyses were not powered for a direct statistical comparison between the two strata. The principal stratum analysis provides the randomization-preserving assessment of whether treatment benefit depends on NfL response. Because patients were classified by NfL response after treatment began, responder-versus-control comparisons are observational; the principal stratum analysis, which classifies patients on pre-treatment characteristics only, was included to provide a randomization-anchored estimate, and is itselfpost hoc. The HEALEY comparator comprised all 329 participants randomized to concurrent regimens, approximately three-quarters of whom received another investigational agent and one-quarter placebo; survival did not differ between active and placebo recipients within either control regimen at the timepoints assessed. By contrast, the supporting observational-cohort analyses in the APST (1,671 evaluable of 2,059 enrolled) and ANSWER ALS (380 evaluable of 742 enrolled) cohorts were prespecified, and their primary and secondary analyses each rejected the null hypothesis in both cohorts. No participant in either cohort received CNM-Au8; approximately 55% and 69% respectively were receiving riluzole. These cohorts establish that NfL trajectory is prognostic at the individual level; whether a treatment’s effect on NfL predicts its effect on survival is addressed by the trial analyses described above. FDA accepted NfL reduction as reasonably likely to predict clinical benefit in SOD1-ALS in the context of the tofersen accelerated approval; the acceptability of a surrogate endpoint is determined program by program, and FDA has made no such determination for CNM-Au8.