NIMBLE
(2026)Objective
To evaluate complement C5-targeted therapies — cemdisiran (C5-targeting siRNA) monotherapy, pozelimab (C5 antibody) monotherapy, and their combination — versus placebo in AChR/LRP4 antibody-positive generalised myasthenia gravis, assessing these approaches as alternatives to existing complement inhibitors.
Study Summary
• The primary endpoint was change from baseline in MG-ADL at week 24 (mITT population); no values, effect sizes, or p-values were provided.
• Reported data are limited to study design (phase 3, randomised, double-blind, placebo-controlled, 86 centres, 13 countries).
Intervention
Cemdisiran (C5-targeting siRNA) monotherapy, pozelimab (C5 antibody) monotherapy, or cemdisiran plus pozelimab combination therapy, versus placebo.
Inclusion Criteria
AChR or LRP4 antibody-positive generalised myasthenia gravis with MG-ADL ≥6.
Study Design
Arms: Cemdisiran monotherapy vs Pozelimab monotherapy vs Cemdisiran + Pozelimab combination vs Placebo (patient counts per arm not reported in source)
Outcome
• No secondary or safety outcome data were available.
Bottom Line
Results were not reported in the available source abstract; clinical conclusions cannot be drawn from the provided text. The trial was designed to test C5-targeted siRNA and antibody approaches (alone and combined) as alternatives to existing complement inhibitors in generalised myasthenia gravis.
Major Points
- Phase 3, randomised, double-blind, placebo-controlled trial conducted at 86 centres across 13 countries.
- Four-arm design: cemdisiran (C5-targeting siRNA) monotherapy, pozelimab (C5 antibody) monotherapy, cemdisiran plus pozelimab combination therapy, and placebo.
- Enrolled AChR/LRP4 antibody-positive generalised myasthenia gravis patients with MG-ADL ≥6.
- Primary endpoint: change from baseline in MG-ADL at week 24 in the mITT population.
- No efficacy, safety, or quantitative outcome data were available in the source abstract.
Study Design
- Study Type
- Randomised controlled trial (phase 3)
- Randomization
- Yes
- Blinding
- Double-blind
- Follow-up
- At least 24 weeks (primary endpoint at week 24)
- Centers
- 86
- Countries
- 13 countries (specific countries not reported in source)
Primary Outcome
Definition: Change from baseline in MG-ADL (Myasthenia Gravis Activities of Daily Living) in the mITT population
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| - |
Citation
Lancet. 2026. doi:10.1016/S0140-6736(26)00690-2. PMID 42030965.