Cemdisiran Looks Promising for Generalized Myasthenia Gravis

Topline results were announced from a phase 3 trial evaluating cemdisiran in adults with generalized myasthenia gravis (gMG).

Cemdisiran is a subcutaneously-administered, small interfering RNA therapeutic that reduces the production of complement factor 5 (C5) in the liver. In the NIMBLE trial (ClinicalTrials.gov Identifier: NCT05070858), patients with anti-acetylcholine receptor (AChR) antibody-positive symptomatic gMG were randomly assigned to receive placebo every 4 weeks (n=59) or cemdisiran, either as monotherapy (600mg every 12 weeks; n=64) or in combination with pozelimab, a C5 antibody (cemdisiran 200mg + pozelimab 200mg every 4 weeks; n=67).

The primary endpoint was the change from baseline in Myasthenia Gravis-Activities of Daily Living (MG-ADL) total score at week 24. The total MG-ADL score ranges from 0 to 24 points, with higher scores indicating greater functional impairment and disability.

Findings showed treatment with cemdisiran was associated with a statistically significant improvement in MG-ADL total score compared with placebo (placebo-adjusted treatment difference: cemdisiran monotherapy: -2.30 [P =.0005]; cemdisiran-pozelimab: -1.74 [P =.0086]). The study also met a key secondary endpoint demonstrating a significant improvement in the Quantitative Myasthenia Gravis total score (placebo-adjusted treatment difference: cemdisiran monotherapy: -2.77 [P =.0015]; cemdisiran-pozelimab: -1.86 [P =.0348]).

Treatment with cemdisiran monotherapy resulted in an average of 74% complement inhibition, while the combination treatment led to nearly 99% inhibition of complement activity. Although the use of complement inhibitors may increase a patient’s susceptibility to serious meningococcal infections, none were reported during the NIMBLE study. 

“The NIMBLE trial results underscore the potential for cemdisiran to offer a best-in-class profile for those suffering with myasthenia gravis, providing for robust efficacy with a convenient quarterly subcutaneous administration,” said George D. Yancopoulos, MD, PhD, Board co-Chair, President and Chief Scientific Officer at Regeneron. “The potential for best-in-class efficacy with less than complete complement blockade with cemdisiran monotherapy may also provide for a more favorable safety profile.”

According to the Regeneron, full study results will be presented at an upcoming medical meeting. The Company expects to submit an application for cemdisiran monotherapy in the treatment of gMG with the Food and Drug Administration in the first quarter of 2026.

This article originally appeared on MPR