At the 2026 American Association of Neuromuscular and Electrodiagnostic Medicine meeting, researchers presented a prespecified exploratory analysis of the phase III NIMBLE trial showing that cemdisiran, an investigational small interfering RNA therapy that targets complement component 5, was associated with fewer hospitalizations than placebo in patients with generalized myasthenia gravis. The analysis focused on the cemdisiran monotherapy group (79 participants) versus placebo (72 participants).
During the 24-week double-blind period, 3.8% of cemdisiran-treated patients were hospitalized for any reason, compared with 15.3% of placebo-treated patients. Myasthenia gravis-related hospitalizations occurred in one cemdisiran patient versus 13 hospitalizations involving 11 placebo patients, and cumulative days of such hospitalizations were 1 day versus 92 days. Myasthenic crises, including impending crises, were reported in 3 cemdisiran patients and 11 placebo patients, and rescue therapy was used in 2 versus 11 patients. Historical hospitalization rates in the six months before randomization were similar between groups.
Adverse events occurred in 69% of the cemdisiran group, most commonly upper respiratory tract infection; no serious or meningococcal infections were observed, and no deaths occurred during the treatment period. Two deaths occurred after the double-blind period, one of which was considered treatment-related by the investigator but not by the sponsor. The NIMBLE trial had already met its primary endpoint of improved Myasthenia Gravis-Activities of Daily Living score at 24 weeks.
In an accompanying editorial, Raffaele Iorio of Policlinico Gemelli and Catholic University in Rome noted that the results suggest clinical benefit may be possible without complete complement blockade, potentially preserving immune defense against encapsulated bacteria. He also raised a concern specific to the siRNA mechanism: cemdisiran suppresses hepatic C5 mRNA production for roughly three months after each injection, a pharmacological effect that cannot be quickly reversed if intact complement activity is urgently needed. Regeneron Pharmaceuticals said regulatory applications for cemdisiran have been accepted by the FDA and the European Medicines Agency, with an FDA decision expected in November 2026 and a European Commission decision anticipated in 2027.