CNM-Au8 Reduces Mortality in ALS, Prenatal Exposure to ASMs Increases Neurodevelopmental Disorders, FDA Grants Tentative Approval to FT218

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Newly announced interim data from the RESCUE-ALS clinical trial (NCT04098406) showed that treatment with CNM-Au8 (Clene Nanomedicine), an investigational suspension of clean-surfaced, catalytically active gold nanocrystals, resulted in significant survival benefit among patients with amyotrophic lateral sclerosis (ALS).Previously reported at the 2022 American Academy of Neurology (AAN) Annual Meeting, April 2-7, the updated results included data through the latest vital status observation with a cut-off of July 5, 2022. Using unadjusted Kaplan-Meier survival analyses obtained for 43 of 45 participants, treatment with CNM-Au8 resulted in 70% decreased risk of death compared with those initially randomized to placebo. When comparing active vs placebo groups, 5 deaths were reported for those on CNM-Au8 (n = 23) compared with 14 deaths observed in those randomized to placebo (n = 22). Median survival from randomization in the CNM-Au8 group was undefined due to insufficient mortality events, and median survival in the placebo group was 23.1 months.

Using a cohort of 4.5 million mother-child pairs, data from new research show robust and dose-dependent associations between prenatal exposure to antiseizure medications (ASMs) topiramate (Topamax; Janssen) and valproate to neurodevelopmental disorders such as autism spectrum disorder (ASD) and intellectual disability (ID). Additionally, ASM duotherapies, except lamotrigine with levetiracetam, were similarly associated with neurodevelopmental disorders.Results showed that among unexposed children of mothers with epilepsy, the 8-year cumulative incidence of ASD and ID was 1.5% and 0.8%, respectively, while in children of mothers with epilepsy exposed to topiramate, it was 4.3% and 3.1%. Similarly, the 8-year cumulative incidence of ASD and ID for valproate-exposed children was 2.7% and 2.4%, respectively. Over the 8-year observed period, the adjusted hazard ratios (aHRs) of ASD were 2.8 (95% CI, 1.4-5.7) and 2.4 (95% CI, 1.7-3.3), respectively for the topiramate and valproate groups, respectively. In terms of ID, the aHRs were 3.5 (95% CI, 1.4-8.6) for those exposed to topiramate and 2.5 (95% CI, 1.7-3.7) for those exposed to valproate.

The FDA has granted tentative approval to Avadel Pharmaceuticals’ extended-release oral suspension formulation of sodium oxybate, marketed as Lumryz, for the treatment of excessive daytime sleepiness (EDS) or cataplexy in adults with narcolepsy.1 Previously, the therapy was known as FT218. The new drug application (NDA) was supported by data from the phase 3 REST-ON study, which was held under a special protocol assessment agreement with the FDA. Investigators, led by Clete A. Kushida, MD, PhD, director, Stanford Center for Human Sleep Research, randomly assigned 222 patients with narcolepsy type 1 or type 2, all aged 16 years or older, to receive uptitration doses of 4.5 g, 6 g, 7.5 g, and 9 g of FT218 or placebo over the course of a 3-week screening period, a 13-week treatment period, and a 1-week follow-up period. The study met all 3 of its primary end points of change from baseline in mean sleep latency on the Maintenance of Wakefulness test, Clinical Global Impression Improvement, and weekly cataplexy attacks within the 6-, 7.5-, and 9-g groups.

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