Overviewing Phase 3 NIMBLE Study of Cemdisiran in Generalized Myasthenia Gravis: Tuan Vu, MD

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"The [NIMBLE] study looked at the placebo group, cemdisiran alone, the combination of cemdisiran and pozelimab, and then looked at a pozelimab arm alone to see what the contribution of the 2 components is. As it turned out, cemdisiran by itself was pretty effective, and the combination did not add any additional advantage over it."

Cemdisiran (Regeneron Pharmaceuticals) is a novel small interfering RNA (siRNA) therapeutic that durably reduces circulating levels of complement factor 5 (C5), allowing for every 3 months dosing. The investigational therapy is currently being evaluated in the phase 3 NIMBLE trial (NCT05070858) among adults living with generalized myasthenia gravis (gMG). At the recently concluded 2026 American Academy of Neurology (AAN) Annual Meeting, held April 18–22 in Chicago, Illinois, neuromuscular expert Tuan Vu, MD, a professor in the Department of Neurology at the University of South Florida Morsani College of Medicine, presented new data from the pivotal trial.¹

By design, NIMBLE is an ongoing randomized, double-blind, placebo-controlled trial assessing the efficacy and safety of cemdisiran, alone or in combination with pozelimab (Regeneron), in patients with anti-acetylcholine receptor antibody-positive gMG. Participants were randomized to receive subcutaneous cemdisiran every 12 weeks, cemdisiran plus pozelimab every 4 weeks, pozelimab alone every 4 weeks, or placebo. The primary end point evaluated change in Myasthenia Gravis Activities of Daily Living total score from baseline to week 24, with change in Quantitative Myasthenia Gravis total score serving as a key secondary end point.

At AAN 2026, Vu, who also serves as the division director of Neuromuscular Medicine EMG Laboratories, spoke with NeurologyLive^® to further outline the rationale and findings from the phase 3 NIMBLE trial. Unlike currently available C5 inhibitors that directly target the C5 molecule, he noted that cemdisiran works by preventing the hepatic production of C5, representing a distinct approach to complement inhibition. According to Vu, cemdisiran alone demonstrated meaningful efficacy, whereas the addition of pozelimab did not provide incremental benefit. He also discussed the therapy’s safety profile, noting limited liver-related concerns and mild hypersensitivity events during the randomized controlled period.

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REFERENCES
1. Cemdisiran, Dosed Subcutaneously Every 12 Weeks, Demonstrates Rapid, Deep and Sustained Disease Control in Generalized Myasthenia Gravis (gMG) Phase 3 Trial. News release. April 21, 2026. Accessed May 14, 2026. https://investor.regeneron.com/news-releases/news-release-details/cemdisiran-dosed-subcutaneously-every-12-weeks-demonstrates