Regeneron Pharmaceuticals reported positive topline results from the Phase 3 NIMBLE trial evaluating investigational cemdisiran, an siRNA targeting complement factor 5 (C5), as monotherapy for adults with generalized myasthenia gravis (gMG). The trial, involving patients with anti-acetylcholine receptor antibodies, randomized participants to receive cemdisiran (600 mg subcutaneously every 12 weeks), a cemdisiran-pozelimab combination (200 mg each every 4 weeks), or placebo.
Cemdisiran monotherapy achieved 74% complement inhibition and met the primary endpoint, demonstrating a placebo-adjusted improvement of -2.30 points (p=0.0005) in the Myasthenia Gravis Activities of Daily Living (MG-ADL) total score at week 24, reflecting better daily functioning in areas like speech, swallowing, breathing, and mobility. The key secondary endpoint, change in Quantitative Myasthenia Gravis (QMG) score, showed a -2.77-point improvement (p=0.0015). Additionally, 76.6% of cemdisiran patients achieved a ≥3-point MG-ADL reduction (relative risk 1.84, p=0.0001), and 48.4% saw a ≥5-point QMG reduction (relative risk 2.67, p=0.0006), outperforming historical C5 inhibitors’ ranges of -1.6 to -2.1 points in MG-ADL.
The cemdisiran-pozelimab combination, with nearly 99% complement inhibition, also met endpoints but was numerically inferior to monotherapy (-1.74 MG-ADL, p=0.0086; -1.86 QMG, p=0.0348). Safety data indicated no meningococcal infections or treatment discontinuations due to adverse events in the cemdisiran arm through week 24. Treatment-emergent adverse events occurred in 69% of cemdisiran patients versus 77% placebo, with serious events lower (3% vs. 14%). Common events included upper respiratory infections and headaches, with two deaths in the extension period unrelated to study drugs per investigators.
These results suggest cemdisiran offers robust efficacy with partial complement blockade, potentially improving safety over full inhibition needed in diseases like paroxysmal nocturnal hemoglobinuria. Regeneron plans FDA discussions for a Q1 2026 submission, positioning cemdisiran as a convenient quarterly therapy for gMG, affecting ~85,000 U.S. patients with muscle weakness and fatigue. The program extends to other complement-mediated disorders, leveraging Regeneron’s siRNA and antibody platforms under an amended Alnylam agreement, with royalties and milestones for Alnylam. Full data will be presented at a medical meeting, underscoring Regeneron’s innovation in autoimmune treatments.
