siRNA Treatment Shows Efficacy for Generalized Myasthenia Gravis

New results from the phase 3 NIMBLE clinical trial (NCT05070858) show that study participants who received cemdisiran (Regeneron Pharmaceuticals, Tarrytown, NY) monotherapy as treatment for generalized myasthenia gravis (gMG) demonstrated meaningful improvements in symptom control and activities of daily living compared with those who received placebo. Additional results from this trial revealed that primary and secondary end points were achieved in those taking combination therapy with cendisiran and Veopoz (pozelimab; Regeneron Pharmaceuticals, Tarrytown, NY) although these results were numerically inferior to those reported for individuals assigned to cemdisiran monotherapy. A regulatory submission for cemdisiran, a small interfering RNA therapy which reduces circulating levels of complement factor 5, tentatively is planned for the first quarter of 2026, according to a statement released by Regeneron Pharmaceuticals.

NIMBLE was a randomized, double-blind study including 190 adults with anti-acetylcholine receptor positive (AChR+) gMG. Participants were randomly assigned to receive treatment with cemdisiran monotherapy (600 mg every 12 weeks; n=64), cemdisiran + Veopoz (200 mg each, every 4 weeks; n=67), or placebo (n=59). Outcomes were assessed at 24 weeks using the Myasthenia Gravis Activities of Daily Living (MG-ADL) total score as the primary end point and the Quantitative Myasthenia Gravis (QMG) score as a key secondary endpoint.

Key results included:

• MG-ADL score change (primary end point): placebo-adjusted difference of -2.30 with cemdisiran monotherapy (P=0.0005) vs -1.74 with combination therapy (P=0.0086).
• QMG score change (secondary endpoint): placebo-adjusted difference of -2.77 with cemdisiran monotherapy (P=0.0015) vs -1.86 with combination therapy (P=0.0348).
• Response rates: 76.6% of cemdisiran monotherapy–treated participants achieved a ≥3-point MG-ADL reduction vs 65.7% with combination therapy and 44.1% with placebo.
• Complement activity inhibition: cemdisiran monotherapy treatment was associated with 74% inhibition while combination therapy was associated with 99% inhibition.

Treatment-emergent adverse events (TEAEs) occurred in 69% of cemdisiran monotherapy–treated participants, 81% of combination therapy–treated participants, and 77% of placebo-treated participants, which were most commonly upper respiratory tract infections and headaches. No meningococcal infections or treatment discontinuations occurred in the cemdisiran monotherapy arm. According to Regeneron Pharmaceuticals, detailed trial data will be presented at an upcoming medical meeting.

Source: Regeneron Pharmaceuticals. Regeneron announces positive results from phase 3 trial in generalized myasthenia gravis. Investor.regeneron.com. Published August 26, 2025. Accessed August 29, 2025. https://investor.regeneron.com/news-releases/news-release-details/regeneron-announces-positive-results-phase-3-trial-generalized