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FDA and EMA accept applications for higher dose regimen of Nusinersen in SMA – Biogen

Biogen Inc. announced that the FDA has accepted the company’s supplemental New Drug Application (sNDA) and the EMA has validated the application for a higher dose regimen of nusinersen for spinal muscular atrophy (SMA). The higher dose regimen of nusinersen comprises a more rapid loading regimen, two 50 mg doses 14 days apart, and higher maintenance regimen, 28 mg, every 4 months, compared to the approved nusinersen regimen (Spinraza ). These applications are based on data from the DEVOTE study, which demonstrate the potential for the investigational higher dose regimen of nusinersen to advance the treatment of SMA.
DEVOTE (NCT04089566) was a Phase II/III randomized, controlled, dose-escalating study designed to evaluate the safety, tolerability, pharmacokinetics and efficacy of nusinersen when administered at a higher dose (50/28 mg). The study enrolled 145 participants across ages and SMA types at approximately 42 sites around the world. DEVOTE includes an open-label safety evaluation cohort (Part A), a double-blind, active control randomized treatment cohort (Part B), followed by an open-label treatment cohort (Part C) to assess the safety and tolerability of transitioning participants from the currently approved dose of Spinraza 12 mg to the higher dose regimen being tested in the study.
Part B was comprised of a pivotal cohort in treatment-naïve patients with infantile-onset SMA (n=75), and a supportive cohort in treatment-naïve patients with later-onset SMA (n=24). The primary endpoint of Part B measured the change from baseline on CHOP-INTEND at six months comparing the higher dose regimen of nusinersen to a matched, untreated sham control group from the Phase III ENDEAR study. ENDEAR is one of the two pivotal studies that formed the basis of regulatory approval for Spinraza 12 mg.
Part C was an open-label evaluation of the higher dose regimen in children and adults who transitioned from Spinraza 12 mg to the 50/28 mg regimen (n=40).
Dr. Stephanie Fradette, Head of the Neuromuscular Development Unit at Biogen said. “This milestone reflects our steadfast commitment to advance treatment options for individuals with SMA, and we expect that this higher dose regimen will offer meaningful benefits to patients and their families. We are deeply thankful for the unwavering support of the trial participants, their families, site staff, and the SMA community without whom these advancements would not have been possible.”
“Continued progress to improve upon the remarkable initial successes in SMA necessitates an innovative approach,” said Dr. Thomas Crawford, co-director of the Muscular Dystrophy Association Clinic at Johns Hopkins Medicine. “ Results from the DEVOTE study have shown us that the higher dose regimen of nusinersen can enable meaningful clinical benefits while maintaining a safety profile broadly consistent with the approved 12 mg regimen.”