What clinops professionals need to know
The Phase III NIMBLE trial demonstrated that cemdisiran, given once every 12 weeks, achieved significant improvements in MG-ADL scores in patients with generalized myasthenia gravis, meeting both primary and secondary endpoints. A combination of cemdisiran and pozelimab (cemdi-poze) achieved nearly complete complement inhibition, but cemdisiran monotherapy performed comparably with less intensive dosing. Safety and tolerability were favorable, with a quarterly subcutaneous administration offering potential operational advantages for long-term patient management. Regeneron plans a US regulatory submission for cemdisiran in 2026, with additional supportive efficacy data from the ACCESS-1 trial in paroxysmal nocturnal hemoglobinuria.
Regeneron has announced positive results from the Phase III NIMBLE clinical trial (NCT05070858) of investigational cemdisiran, a small interfering RNA (siRNA) that reduces circulating levels of complement factor 5 (C5), in adults with generalized myasthenia gravis (gMG).1
Phase III NIMBLE trial results
According to the results, cemdisiran monotherapy, at a subcutaneous dose of every three months, met NIMBLE’s primary and key secondary endpoints, demonstrating a 2.3-point placebo-adjusted improvement in Myasthenia Gravis Activities of Daily Living (MG-ADL) total score.
Efficacy of cemdisiran and cemdi-poze combination
NIMBLE also evaluated cemdisiran alongside pozelimab, a C5 antibody. The combination, dubbed cemdi-poze, resulted in nearly 99% inhibition of complement activity, achieving its primary and key secondary endpoints. Cemdisiran monotherapy performed numerically better across these endpoints, including an average of 74% inhibition of complement activity.
In a press release, L. Andres Sirulnik, MD, PhD, senior vice president and hematology clinical development unit head at Regeneron, said: “Our pipeline approach to treating complement-mediated diseases allows us to tailor treatment to the underlying disease biology. The results of the NIMBLE trial confirm that, in myasthenia gravis, robust efficacy can be achieved without complete complement blockade, whereas in other diseases such as paroxysmal nocturnal hemoglobinuria (PNH), complete inhibition is likely to be necessary. We have previously released data from the lead-in portion of our PNH Phase III trial, supporting the potential for the cemdi-poze combination to deliver best-in-class efficacy in PNH. We are also investigating systemic administration of both cemdisiran monotherapy and the cemdi-poze combination in our Phase III program for geographic atrophy secondary to age-related macular degeneration.”
Study design and endpoints
The NIMBLE trial is a randomized, double-blind, placebo-controlled study assessing cemdisiran and cemdi-poze in patients with gMG who have antibodies to the acetylcholine receptor and may be receiving standard of care immunosuppressants.
