Cemdisiran Linked With Fewer Hospitalizations in Myasthenia Gravis Study

Cemdisiran, an investigational small interfering RNA (siRNA) therapeutic targeting complement component 5 (C5), led to fewer hospitalized myasthenia gravis patients compared with placebo, a prespecified exploratory analysis of NIMBLE trial data showed.

During the trial’s 24-week double-blind treatment period, fewer participants in the cemdisiran group were hospitalized for any reason compared with participants in the placebo group (3.8% vs 15.3%), reported Ali Habib, MD, of University of California Irvine, at the 2026 American Association of Neuromuscular and Electrodiagnostic Medicine in Orlando.

“Fewer participants in the cemdisiran arm experienced myasthenia gravis-related hospitalization compared to the placebo arm,” Habib added. “The total number of days for hospitalization was lower in the treatment arm compared to the placebo arm. The use of rescue therapy was lower in the treatment arm compared to the placebo arm. And in general, much in keeping with the rest of the study, patients treated with cemdisiran tolerated it well.”

Cemdisiran is a subcutaneous siRNA therapy that reduces C5 production in the liver. The phase III NIMBLE trial investigated cemdisiran, alone or in combination with the C5 antibody pozelimab (Veopoz), versus placebo. Both cemdisiran groups met the study’s primary endpoint of improvement in Myasthenia Gravis-Activities of Daily Living (MG-ADL) score at 24 weeks.

Adverse events occurred in 69% of participants in the cemdisiran group, the most common being upper respiratory tract infection. No serious or meningococcal infections were seen. No deaths were reported during the double-blind treatment period, but two deaths occurred afterward: one, due to pneumonia, was considered treatment-related by the investigator but not by the sponsor.

NIMBLE participants had an MG-ADL score of 6 or greater. About 95% of participants had anti-acetylcholine receptor (AChR) antibodies.

The exploratory analysis descriptively compared the number and duration of hospitalizations in NIMBLE, including those resulting from myasthenic crisis, Habib explained. “Given the results observed with cemdisiran monotherapy in terms of the primary endpoint, we focused on comparing the cemdisiran monotherapy and placebo treatment groups,” he pointed out.

The cemdisiran group had 79 participants and the placebo group had 72. In the 6 months before randomization, both groups had a similar proportion of historical hospitalizations due to myasthenia gravis: 8.9% in the cemdisiran group and 11.1% in the placebo group.

Mean age in the cemdisiran group was 53 years and 55.7% were women; they received 600 mg of subcutaneous cemdisiran once every 12 weeks. The placebo group had a mean age of 49 and 62.5% were women.

Three participants in the cemdisiran group experienced a myasthenic crisis (including impending crisis), as did 11 in the placebo group, Habib reported. Two participants in the cemdisiran group had rescue therapy administered, compared with 11 in the placebo group.

The cemdisiran group had one myasthenia gravis-related hospitalization; the placebo group had 13 involving 11 participants. Cumulative days of myasthenia gravis-related hospitalizations totaled 1 day in the cemdisiran group and 92 days in the placebo group.

NIMBLE findings suggest that clinical benefits could occur without complete complement blockade, noted Raffaele Iorio, MD, PhD, of Policlinico Gemelli and Catholic University in Rome, in an editorial published in The Lancet earlier this year. “Preservation of residual complement activity might provide a reserve of immune defense against encapsulated bacteria — a potential benefit over existing C5 inhibitors,” he pointed out.

A potential concern may be the siRNA mechanism, Iorio observed. “Unlike protein-based C5 inhibitors, whose effects are reversible once drug levels decline after discontinuation (albeit over varying timescales across molecules), cemdisiran suppresses hepatic C5 mRNA production for approximately 3 months after each injection, a pharmacological commitment that cannot easily be titrated or rapidly reversed if intact complement activity is urgently required,” he wrote.

Both the FDA and the European Medicines Agency have accepted regulatory applications for cemdisiran to treat generalized myasthenia gravis patients with anti-AChR antibodies, drug developer Regeneron Pharmaceuticals said. The FDA’s decision is expected in November 2026; the European Commission decision is anticipated in 2027.