FDA Accepts sNDA for Higher Dose Nusinersen, Tofersen Demonstrates Real-World Efficacy, Nipocalimab Gains Priority Review

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Welcome to this special edition of Neurology News Network. I'm Marco Meglio.

According to a new announcement, the FDA has accepted Biogen’s supplemental new drug application (sNDA) for a higher, potentially more efficacious dose regimen of nusinersen (Spinraza) for patients with spinal muscular atrophy (SMA). The company also reported that the European Medicines Agency (EMA) has validated the application for the higher dose as well. The higher dose nusinersen regimen includes a faster loading phase with two 50 mg doses administered 14 days apart, followed by a higher maintenance dose of 28 mg every 4 months, compared to the standard approved nusinersen regimen. The regulatory submission was based on findings from the phase 2/3 DEVOTE study (NCT04089566), a randomized, controlled, dose-escalating trial that comprised of 145 participants across ages and SMA types at 42 sites around the globe.

A small-scale, single-center observational study showed that treatment with tofersen (Qalsody; Biogen), an FDA-approved medication for patients with amyotrophic lateral sclerosis (ALS) caused by superoxide dismutase 1 (SOD1) gene mutations, can lead to meaningful preservation of function and slowing of motor decline. In addition, the study revealed robust, significant, and sustained reductions in serum and cerebrospinal fluid neurofilaments (NfL), further supporting the role of neurofilaments as therapeutic biomarkers. Tofersen, an antisense oligonucleotide that binds to and facilitates RNase-mediated degradation of SOD1 messenger RNA, was approved in April 2023 as the first and only treatment for SOD1 mutation-mediated ALS, a genetic form of the disease. The study, an investigator-initiated investigational trial, comprised of 7 patients who had a confirmed, pathogenic, mutation in SOD1 and received 100 mg of tofersen via intrathecal administration. The dosing regimen included 3 loading doses at 14-day intervals followed by monthly maintenance doses, the same regimen suggested in the current prescribing label for tofersen.

According to a recent announcement, the FDA has granted priority review to Johnson & Johnson’s investigational monoclonal antibody nipocalimab as a potential treatment for patients with myasthenia gravis (MG), an autoantibody disease. Nipocalimab, designed to bind with high affinity to block FcRn and reduce levels of circulating immunoglobulin G (IgG) antibodies, remains currently under review by the European Medicines Agency. If approved, nipocalimab will be available for antibody-positive patients with MG, including those with anti-acetylcholine (AChR), anti-muscle-specific kinase antibody (MuSK), and anti-low density lipoprotein-related protein 4 (LRP4) subtypes. The agent’s application is supported by the phase 3 Vivacity-MG3 study (NCT04951622), a large-scale trial that demonstrated nipocalimab’s superiority over placebo plus standard-of-care (SOC) therapy over a 24-week period.

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