In 13 countries, including France, the Phase III Nimble trial evaluated cemdisiran, a small interfering RNA (siRNA) targeting complement component 5, administered subcutaneously, in patients with generalised myasthenia gravis with anti-RACh and/or anti-LRP4 antibodies:
- 263 adults were treated for 24 weeks with cemdisiran alone (600 mg every 12 weeks), cemdisiran (200 mg every 4 weeks) combined with pozelimab (an anti-C5 monoclonal antibody), pozelimab alone (200 mg every 4 weeks) or a placebo;
- improvement in the MG-ADL score (primary efficacy endpoint) was significantly greater for cemdisiran alone,
- the combination of the two anti-C5 agents, at lower doses, provided no additional benefit compared with cemdisiran monotherapy,
- the authors also report more marked benefits on the QMG score, the occurrence of myasthenic crises and the frequency of hospitalisations with cemdisiran,
- 69% of patients in the cemdisiran group reported at least one adverse event, a lower rate than in the pozelimab (82%), the cemdisiran-pozelimab group (81%) and the placebo group (77%); the most common was upper respiratory tract infection,
- no serious infections (notably meningococcal) occurred in the cemdisiran group.
