Regeneron Pharmaceuticals (Nasdaq: REGN) reported that cemdisiran, its investigational siRNA therapeutic, met both the primary and key secondary endpoints in the Phase III NIMBLE trial in generalized myasthenia gravis, with results published simultaneously in The Lancet and presented at the American Academy of Neurology annual meeting.
The NIMBLE trial is a randomized, double-blind, placebo-controlled study enrolling anti-acetylcholine receptor antibody-positive adults with gMG, evaluating cemdisiran monotherapy as well as its combination with the C5 antibody pozelimab.
At week 24, patients receiving cemdisiran 600 mg subcutaneously every 12 weeks (n=64) showed a 4.5-point improvement from baseline on the Myasthenia Gravis-Activities of Daily Living scale, versus 2.2 points for placebo (n=59), a placebo-adjusted difference of 2.3 points (p<0.001). On the physician-administered Quantitative Myasthenia Gravis score, cemdisiran produced a 4.2-point improvement versus 1.5 points for placebo, a 2.8-point adjusted difference (p=0.002). Notably, 76.6% of cemdisiran-treated patients achieved a clinically meaningful threshold of at least a 3-point MG-ADL improvement, compared with 44.1% on placebo, and improvements were detectable within two weeks of the first dose. The safety profile was broadly favorable: treatment-emergent adverse events occurred in 69.2% of cemdisiran patients versus 77.1% on placebo, with no serious infections, meningococcal events, or deaths during the double-blind period.
The gMG treatment landscape already includes approved C5 inhibitors — eculizumab and ravulizumab — both of which block C5 at the protein level. Ravulizumab's Phase III data in gMG, published in 2022, showed placebo-adjusted MG-ADL improvements in the range of 1.6 to 2.1 points across approved C5 agents at their respective primary analyses, a benchmark Regeneron cites directly in its press release. Cemdisiran's 2.3-point adjusted MG-ADL improvement and the speed of onset within two weeks sit at the upper end of that historical range, though cross-trial comparisons are limited by differences in patient populations, background therapy, and trial design.