Latest NIMBLE Study Results Highlight Progress in gMG Research

In a recent video interview with Applied Clinical Trials, Umesh Chaudhari, executive medical director, global program head of the C5 programs, Regeneron, discussed recently released data from the Phase III NIMBLE clinical trial (NCT05070858), which evaluated the efficacy of cemdisiran monotherapy and a combination of cemdisiran and pozelimab in generalized myasthenia gravis (gMG). The study showed a 2.3-point reduction in the Myasthenia Gravis Activities of Daily Living (MG-ADL) score, indicating improved daily functioning. The combination therapy had a 17% worsening rate, compared to 1% in the cemdisiran monotherapy group. Chaudhari highlighted the trial's robust design, including double-blind, double-dummy protocols, and standardized assessments, which ensured high data quality. The findings suggest that lower complement inhibition levels may be optimal for efficacy, with implications for future research in autoimmune diseases.

Chaudhari: First of all, I wanted to state that we're very excited by the results. There's a number of reasons why. First of all, this is the scientific understanding that has come to fruition now with the role of complement inhibition for patients with myasthenia gravis, the role of a silencing RNA that was evaluated for the first time in patients with myasthenia gravis, and of course, the results themselves.

The results themselves show that patients that received cemdisiran monotherapy had improvements in their activities of daily living, and what we call the Myasthenia Gravis Quantitative assessment. These assessments measure how patients feel and function as pertains to their signs and symptoms of myasthenia gravis and impacting their daily living or in a physical examination performed by the clinician. The reductions were demonstrated through a trial that we did called the NIMBLE study. This study is a study that enrolled patients with myasthenia gravis that were symptomatic and were on background standard of care, so they were on background standards care. When I'll introduce placebo, it's placebo plus background standard of care, or when we when we talk about our treatments such as cemdisiran or the combination, they're on top of standard of care.

The trial was one of the largest Phase III trials in the space, so patients were randomized to either cemdisiran monotherapy, combination of our monoclonal antibody C5 inhibitor called pozelimab, plus cemdisiran, the silencing RNA, and lastly, placebo. The trial included what we call a double blind, double dummy period and what that means is that all patients got blinded injections of these drugs, and they also got it at the same interval, the same volume, to try to maintain the blind and not have an investigator have knowledge of what treatment assignment their patients were assigned to. After 24 weeks, with the rigor that we included in this study, which was the same investigators were asked to do these assessments at the same time of day, with other certain aspects of the protocol to standardize everything, to provide robust data at this end of the 24-week period.