How the NIMBLE Study Supported Adherence With Quarterly Dosing of Cemdisiran

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.

ACT: The quarterly subcutaneous dosing of cemdisiran represents a patient-convenient schedule. How did the NIMBLE trial incorporate adherence monitoring and site coordination to support this less frequent visit model?

Chaudhari: I just want to highlight that it is given quarterly, yes, cemdisiran is given quarterly. We believe that in this space of patients that are treated myasthenia gravis, there's two classes of drugs, FcR inhibitors and complement inhibitors, and within that context, FcR inhibitors are given frequently, I would say, either every week or every two weeks, IV, this new subq formulation out, but it's given cyclic dosing, and complement inhibitors are given IV, often every two weeks, sometimes every eight weeks. There's another one that's given daily as a subq injection, so we think this aspect of it—you mentioned compliance—I like to think of it as a reduction in treatment burden to patients every 12 weeks, a subq administration, and with the potential in the future, we hope to be self-administered, so that that's one aspect.

In terms of the trial, how this was able to incorporate adherence monitoring and site coordination to support less frequent visit model, in fact, as I mentioned previously, the first 24 weeks, we had all patients come in at the same visit, even if the treatment visit schedule was every 12 weeks. Why? Because we had to maintain a double blind, double dummy setting, so even if a patient on cemdisiran was coming in, was getting treatment, active treatment, every 12 weeks, it was intermixed with every four weeks. The four-week, the eight-week of placebo administration, to ensure double blind, double dummy, and ensure the validity and integrity of the trial design.

As you probably you may have seen, the patient discontinuation rate is very low. We were very encouraged by that. That first gives us a sign that the data quality, the adherence was at a high standard, and that was done through sites contacting the patients prior to visits, reminding them what to hold prior to coming in for their assessments. It was something of that nature. There's various other measures, such as reminder cards and other means to try to ensure adherence.