Phase 3 NIMBLE Trial: Cemdisiran Proves Efficacy Treating Patients With Generalized Myasthenia Gravis

In a presentation at the American Academy of Neurology (AAN) 2026 Annual Meeting¹ and an interview with Pharmacy Times², Tuan H. Vu, MD, a professor in the Department of Neurology at USF Health in Tampa, Florida, describes how cemdisiran (Alnylam Pharmaceuticals, Regeneron) monotherapy matched or outperformed cemdisran with pozelimab (Veopoz; Regeneron) in every end point when treating patients with generalized myasthenia gravis (gMG) during the phase 3 NIMBLE trial (NCT05070858).³

Cemdisiran stands out as a potential treatment because it targets C5 messenger RNA rather than the C5 protein itself. Unlike other agents that block the effect of C5 on the postsynaptic membrane, cemdisiran instead reduces the production of C5 available for complement activation. Because of this mechanism of action, it can be administered subcutaneously once every 3 months, Vu explained in the interview.²

NIMBLE is a randomized, double-blind, placebo-controlled, phase 3 trial that was conducted at 86 centers across 13 countries. Enrolled patients were 18 years or older with a diagnosis of gMG, with positive serology for anti-acetylcholine receptor (AChR) or anti-LRP4 antibodies, and a Myasthenia Gravis-Activities of Daily Living (MG-ADL) score of 6 or greater. Vu said that patients were randomly assigned to receive the following: cemdisiran monotherapy (600 mg every 12 weeks; cemdisiran group); pozelimab monotherapy (200 mg every 4 weeks; pozelimab group); a combination of cemdisiran (200 mg every 4 weeks) and pozelimab (200 mg every 4 weeks; combination group); or placebo. Regardless of their assigned groups, all treatments were administered subcutaneously during a 24-week double-blind treatment period.^1,3

NIMBLE’s primary end point was change from baseline in MG-ADL scores at week 24, assessed in the modified intention-to-treat (mITT) primary analysis set, which consisted of the first 245 randomly allocated patients who received any dose of study treatment and had at least 1 post-baseline assessment. Additionally, Vu explained that safety was mainly assessed by recording of treatment-emergent adverse events (AEs) in all patients who received any dose of study treatment.¹

Between January 20, 2022, and July 18, 2025, 390 participants were screened and 284 were randomly assigned to the cemdisiran group (n = 79), pozelimab group (n = 50), combination (n = 80), or placebo group (n = 75). Of the 277 patients who received any study treatment, approximately (n = 263) completed the double-blind treatment period.

Vu reported that, in the mITT primary analysis set at week 24, the least-squares mean change from baseline in MG-ADL total score was greatest in the cemdisiran group (–4.5, n = 64), followed by the combination group (–4.0, n = 67), and the placebo group (–2.2, n = 59). Additionally, placebo-adjusted least-squares mean differences in MG-ADL score at week 24 were –2.3 ([95% CI, –3.6 to –1.0]; p = .0005) and –1.7 ([95% CI, –3.0 to –0.4]; p = .0086) in the cemdisiran and combination groups, respectively.¹

The number of patients with at least 1 reported AE during the double-blind treatment period was 54 in the cemdisiran group, 65 in the combination group, 40 in the pozelimab group, and 54 in the placebo group. The most common AE in the cemdisiran group was upper respiratory tract infection (n = 9). Notably, there were no serious or meningococcal infections that occurred in the cemdisiran group.¹

“[The risk of meningococcal infection] is always a concern. The complement cascade is what we rely on to fight encapsulated bacteria, and blocking it increases the risk of meningococcal meningitis,” Vu explained during the interview. “As discussed, cemdisiran does not block complement completely, so perhaps that provides some degree of protection over time. The study is fairly short, however, so we do not know what the long-term effect will look like over years—that remains to be seen. I do think that for anything involving C5, proper vaccination is still required.”²

Additionally, AEs leading to treatment discontinuation occurred in only 2 participants in the placebo group and 1 participant in the pozelimab group. No deaths occurred during the double-blind treatment period; however, 2 deaths occurred following the double-blind treatment period, of which 1 was assessed as treatment-related by the investigators.¹

From a treatment landscape perspective, these findings from the NIMBLE trial could shift how health care professionals approach managing gMG. If monotherapy with an RNA-targeting agent can deliver strong efficacy, good tolerability, and less frequent dosing, it may become a preferred option and reduce reliance on combination biologic strategies that add cost and complexity without clear benefit. Specifically, pharmacists play an important role in formulary decisions and access considerations. In practice, this means they should be ready to educate both providers and patients, optimize therapy selection, ensure preventive measures (eg, meningococcal vaccination), and monitor long-term safety trends as this treatment approach evolves.

“The NIMBLE study met the primary and key secondary end points with subcutaneous cemdisiran every 3 months, and the combination really didn't add anything more to just monotherapy. Cemdisiran monotherapy achieved robust efficacy while preserving residual complement activity with no waning of efficacy throughout the dosing period. This effect may give us some benefit in terms of, perhaps, reducing the incidence of meningococcal meningitis,” Vu concluded in the AAN presentation. “However, that's a conjecture at this point, and we won't know for sure until after a prolonged observation period. The drug was very well tolerated, with no serious infections, including no meningococcal infections during the double-blind control period.”¹

Watch the full interview with Tuan H. Vu, MD here.

REFERENCES

1. Vu T. PL5 – Clinical Trials Plenary Session: Efficacy and safety of cemdisiran siRNA in myasthenia gravis (NIMBLE): a double-blind, randomized, placebo-controlled, phase 3 trial. Presented at: American Academy of Neurology 2026 Annual Meeting. Chicago, Illinois; April 18-22.

2. Vu T, Ferruggia K. AAN 2026: Expert Insight on Cemdisiran’s Role in Simplifying gMG Care Through Subcutaneous Quarterly Dosing. Pharmacy Times. April 1, 2026. Accessed April 22, 2026. https://www.pharmacytimes.com/view/aan-2026-expert-insight-on-cemdisiran-s-role-in-simplifying-gmg-care-through-subcutaneous-quarterly-dosing

3. A Study to Test How Safe Pozelimab and Cemdisiran Combination Therapy and Cemdisiran Alone Are and How Well They Work in Adult Patients With Generalized Myasthenia Gravis (NIMBLE). ClinicalTrials.gov identifier: NCT05070858. Updated February 12, 2026. Accessed April 22, 2026. https://clinicaltrials.gov/study/NCT05070858