FDA and EMA Accepts Regulatory Applications for Cemdisiran in Generalized Myasthenia Gravis

Both the FDA and European Medicines Agency (EMA) have accepted regulatory applications for Regeneron Pharmaceuticals’ cemdisiran, an investigational small interfering RNA (siRNA) for the treatment of adult patients with anti-acetylcholine receptor (AChR) antibody–positive generalized myasthenia gravis (gMG). If approved, cemdisiran would represent the first siRNA agent indicated for gMG and the first complement-targeting treatment available via subcutaneous quarterly dosing in this population.¹

The FDA accepted the company’s new drug application for cemdisiran under priority review following the use of a priority review voucher, with a PDUFA target action date of November 2026. In addition, the EMA has accepted the Marketing Authorization Application; a decision from the European Commission is anticipated in the second half of 2027. The company also noted that a regulatory submission in Japan is planned for early 2027.

“Generalized myasthenia gravis is a chronic debilitating disease with unpredictable symptoms that impact daily life. While current therapies have managed disease activity, there remains an unmet need for options that achieve rapid and sustained efficacy with reduced treatment burden,” Tuan Vu, MD, professor of neurology at the University of South Florida Morsani College of Medicine, said in a statement.²

Phase 3 NIMBLE Trial

The applications are supported by data from the phase 3 NIMBLE trial (NCT05070858), a global, randomized, double-blind, placebo-controlled study. Eligible adults had symptomatic, AChR antibody–positive gMG; concomitant standard-of-care immunosuppressants. Participants received subcutaneous cemdisiran every 12 weeks or placebo for 24 weeks. The trial also included combination arms with the anti-C5 antibody pozelimab (Regeneron). The primary end point was change from baseline in Myasthenia Gravis–Activities of Daily Living (MG-ADL) score at week 24, with key secondary endpoints including Quantitative Myasthenia Gravis (QMG) score.

At week 24, patients treated with cemdisiran experienced a least squares mean reduction of 4.5 points in MG-ADL total score compared with 2.2 points in the placebo group, corresponding to a placebo-adjusted difference of –2.3 points (P <.001). In addition, a greater proportion of patients receiving cemdisiran achieved clinically meaningful improvement (≥3-point reduction) versus placebo (76.6% vs 44.1%). Improvements were observed as early as 2 weeks and were sustained through the study period, with no apparent waning of effect between doses.

Similarly, cemdisiran demonstrated superiority on QMG, with a mean reduction of 4.2 points compared with 1.5 points for placebo (difference, –2.8; P =.002). Nearly half of treated patients (48.4%) achieved a 5-point or greater improvement versus 19% in the placebo group. These data were published simultaneously in The Lancet and presented at the 2026 American Academy of Neurology (AAN) Annual Meeting, held April 18–22 in Chicago, Illinois.^2,3

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The overall safety profile of cemdisiran appeared comparable to placebo during the double-blind treatment period. Treatment-emergent adverse events (AEs) occurred in 69.2% of patients receiving cemdisiran and 77.1% of those receiving placebo. Common AEs included upper respiratory tract infection, headache, urinary tract infection, and nasopharyngitis, with most events being mild to moderate in severity.

Rates of infection were numerically lower in the cemdisiran group (27%) compared with placebo (40%), and no meningococcal infections or deaths were reported during the double-blind phase. One death because of pneumonia occurred during the extension period in a patient receiving cemdisiran with significant comorbidities and concomitant immunosuppressive therapy.⁴

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.

REFERENCES
1. Cemdisiran Regulatory Submissions Accepted for Review by FDA and EMA for the Treatment of Generalized Myasthenia Gravis (gMG). News release. Regeneron Pharmaceuticals. June 22, 2026. Accessed June 22, 2026. https://newsroom.regeneron.com/news-releases/news-release-details/cemdisiran-regulatory-submissions-accepted-review-fda-and-ema
2. Cemdisiran, Dosed Subcutaneously Every 12 Weeks, Demonstrates Rapid, Deep and Sustained Disease Control in Generalized Myasthenia Gravis (gMG) Phase 3 Trial. Regeneron Pharmaceuticals. News Release. April 21, 2026. Accessed June 22, 2026. https://investor.regeneron.com/news-releases/news-release-details/cemdisiran-dosed-subcutaneously-every-12-weeks-demonstrates
3. Vu T, Habib AA, Jacob S, et al. Efficacy and safety of cemdisiran siRNA in myasthenia gravis (NIMBLE): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet. 2026;407(10540):1712-1725. doi:10.1016/S0140-6736(26)00690-2
4. Regeneron Announces Positive Results from Phase 3 Trial in Generalized Myasthenia Gravis. News release. Regeneron Pharmaceuticals. August 26, 2025. Accessed June 22, 2026. https://investor.regeneron.com/news-releases/news-release-details/regeneron-announces-positive-results-phase-3-trial-generalized