Simdesiran cuts myasthenia gravis symptom score by 4.52 points in phase 3 trial

Key Facts

The phase 3 NIMBLE trial found that simdesiran reduced the mean Myasthenia Gravis Activities of Daily Living (MG-ADL) score by 4.52 points at week 24, compared with 2.22 points with placebo, according to results published by Regeneron. The adjusted difference between the treatments was 2.30 points in favor of the drug, with a p-value of 0.0005. The data cover adults with generalized myasthenia gravis who tested positive for acetylcholine receptor antibodies. The company announced in August 2025 that the trial had met its primary and key secondary efficacy endpoints, then published and presented the detailed results in April 2026. In an update on third-quarter results published on October 30, 2026, Regeneron’s chief executive said the company expected an FDA decision the following month.

On individual response, 76.6% of patients receiving simdesiran achieved a reduction of at least 3 points in MG-ADL at week 24, compared with 44.1% in the placebo group. The relative risk of response was 1.84, with a p-value of 0.0001, according to Regeneron data. These percentages represent another secondary trial outcome and do not replace the mean change in the score, which was the primary outcome cited above. On the Quantitative Myasthenia Gravis (QMG) score, which assesses disease severity, the mean fell by 4.24 points with the drug and 1.46 points with placebo. The adjusted difference in QMG was 2.77 points in favor of treatment, with a p-value of 0.0015.

An additional QMG result showed that 48.4% of patients who received simdesiran achieved a reduction of at least 5 points at week 24, compared with 19% in the placebo group. Trial groups ranged from 64 patients who received the drug alone, to 67 who received the combination of simdesiran and pozelimab, and 59 who received placebo. All patients in the drug-alone group completed treatment through week 24, compared with 96% in the combination group and 90% in the placebo group. The drug-alone group received a 600 mg subcutaneous injection every 12 weeks. The combination group received 200 mg each of simdesiran and pozelimab every 4 weeks.

Serious adverse events were reported in 3% of patients receiving simdesiran, 9% of the combination group and 14% of the placebo group, the company said. No deaths were recorded during the 24-week placebo-controlled period. Regeneron said clinically meaningful improvement in MG-ADL appeared within two weeks among patients receiving the drug, with a mean 2.5-point reduction from baseline in a prespecified exploratory assessment. In the NIMBLE trial, the drug alone was associated with mean complement activity inhibition of 74%, while inhibition was about 99% when combined with pozelimab. Simdesiran, an RNA interference therapy, is designed to reduce circulating levels of complement component C5.

The company put the results in the context of earlier registration trials of approved therapies targeting C5, in which adjusted improvement versus placebo ranged from 1.6 to 2.1 points on MG-ADL and from 2.0 to 3.0 points on QMG. Primary analyses in those trials were generally conducted at week 12 or 26, making the comparison descriptive across separate studies rather than a direct randomized comparison. Regeneron published the detailed NIMBLE results in The Lancet and first presented them in a plenary session at the American Academy of Neurology’s annual meeting. Myasthenia gravis is a rare, chronic autoimmune disease, and the company estimates that about 85,000 people in the United States have it. Under an amended licensing agreement in June 2024, Regeneron secured a global license to develop simdesiran as a standalone treatment or in combination with antibodies against C5.

Before the expected date, the FDA had accepted the therapy’s application for priority review on June 22, 2026, and set November 2026 as the target date for a decision, according to Regeneron. The European Medicines Agency also accepted the regulatory application, and the company expects a European Commission decision in the second half of 2027. Regeneron plans to file a regulatory application in Japan in early 2027. Acceptance for review means the application has entered the regulatory assessment process, but does not constitute marketing approval for the drug. Regeneron shares closed at $927.89 on October 30, 2026, compared with a close of $818.77 in the previous session, according to EL7 data.