Cemdisiran, a new investigational treatment for generalized myasthenia gravis (gMG), showed successful results in its Phase 3 NIMBLE trial, as announced by RegeneronThis trial confirmed that cemdisiran monotherapy, administered subcutaneously every three months, met its primary and key secondary endpoints, showing a significant improvement in patients' daily living activities. The study demonstrated that cemdisiran, an siRNA designed to reduce complement factor 5 (C5), led to a 2.3-point placebo-adjusted improvement on the Myasthenia Gravis Activities of Daily Living (MG-ADL) total score, a patient-reported measure of daily function. This result is numerically better than the 1.6 to 2.1-point improvements seen with other approved C5 inhibitor therapies. The trial also evaluated a combination of cemdisiran and pozelimab, a C5 antibody, which also met its endpoints but was numerically less effective than the cemdisiran monotherapy.

The findings from the NIMBLE trial highlight Regeneron's strategic approach to treating complement-mediated diseases by tailoring therapies to the specific disease biology. According to Regeneron leadership, the robust efficacy of cemdisiran in gMG demonstrates that complete complement blockade is not always necessary for effective treatment, which may also lead to a more favorable safety profile. While cemdisiran monotherapy showed strong results in gMG, the company is also investigating the cemdi-poze combination for other conditions where more complete inhibition may be required, such as paroxysmal nocturnal hemoglobinuria (PNH) and geographic atrophy. The NIMBLE trial evaluated adults with symptomatic gMG who had antibodies to the acetylcholine receptor. Patients were given either cemdisiran every 12 weeks, the cemdi-poze combination every 4 weeks, or a placebo every 4 weeks.

In addition to the primary MG-ADL endpoint, cemdisiran also showed a significant placebo-adjusted improvement of 2.77 points on the Quantitative Myasthenia Gravis (QMG) total score, a physician-administered assessment of muscle function. Both treatment arms showed marked improvement in patient symptoms, but cemdisiran consistently performed better. In terms of safety, cemdisiran was well-tolerated. Treatment-emergent adverse events were less frequent in the cemdisiran arm compared to the combination and placebo arms, and there were no serious adverse events leading to discontinuation of treatment. The most common adverse events included upper respiratory tract infections, headache, and urinary tract infections. No meningococcal infections were reported in any of the patients. Based on these positive outcomes, Regeneron plans to submit a regulatory application for cemdisiran monotherapy to the U.S. Food and Drug Administration (FDA) in the first quarter of 2026. This potential new therapy offers a convenient, quarterly subcutaneous administration, which could significantly improve the quality of life and long-term management for patients living with gMG.