Positive Cemdisiran Phase 3 Data Paves Way for Myasthenia Gravis BLA Submission

Cemdisiran monotherapy has met its trial’s key endpoints and demonstrated significant improvements over placebo in Myasthenia Gravis Activities of Daily Living (MG-ADL) total score, paving the way for Regeneron’s planed Biologics License Application submission for the first quarter of 2026.1

“Our pipeline approach to treating complement-mediated diseases allows us to tailor treatment to the underlying disease biology,” L. Andres Sirulnik, MD, PhD, Senior Vice President and Hematology Clinical Development Unit Head at Regeneron, said in a statement.1 “The results of the NIMBLE trial confirm that, in MG, robust efficacy can be achieved without complete complement blockade, whereas in other diseases such as paroxysmal nocturnal hemoglobinuria (PNH), complete inhibition is likely to be necessary. We have previously released data from the lead-in portion of our PNH Phase 3 trial, supporting the potential for the cemdisiran and pozelimab (cemdi-poze) combination to deliver best-in-class efficacy in PNH.2 We are also investigating systemic administration of both cemdisiran monotherapy and the cemdi-poze combination in our Phase 3 program for geographic atrophy secondary to age-related macular degeneration.”

Cemdisiran is an siRNA that reduces circulating levels of complement factor 5 (C5) and is being evaluated as monotherapy and in the cemdi-poze combination (200 mg cemdisiran and 200 mg pozelimab) in the Phase 3 NIMBLE trial in adults with generalized MG (gMG) who have antibodies to the acetylcholine receptor (anti-AChR) and may be receiving standard of care immunosuppressants based on the investigator’s discretion. Pozelimab works by binding to and inhibiting complement factor C5.

NIMBLE is a double-blind trial, randomly assigned adults with gMG to either cemdisiran 600 mg monotherapy (n = 64) every 12 weeks, cemdi-poze (n = 67) every 4 weeks, or placebo (n = 59) every 4 weeks for a 24-week treatment period. Its primary endpoint was total score changes from baseline to week 24 in the MG-ADL total score, a patient-reported questionnaire that measures daily functions impacted by gMG, and its key secondary endpoint was total score changes from baseline in the Quantitative Myasthenia Gravis (QMG) total score, a physician-administered assessment evaluating vision, speaking/swallowing, breathing and limb function.

All told, both treatment groups outperformed placebo, with greater effects observed in the monotherapy group. At the conclusion of the 24-week period, investigators recorded placebo-adjusted treatment differences of –2.30 (P = .0005) and –1.74 (P = .0086) for the cemdisiran monotherapy and cemdi-poze groups, respectively, on MG-ADL. Regeneron also noted that cemdisiran was associated with an average of 74% inhibition of complement activity and cemdi-poze resulted in nearly 99% inhibition of complement activity. Detailed data from NIMBLE will be presented at an upcoming medical meeting.1

In terms of safety, treatment-emergent adverse events (TEAEs) occurred in 69% of patients treated with cemdisiran, 81% with cemdi-poze, and 77% with placebo; these were serious in 3%, 9%, and 14% of the groups, respectively. Common TEAEs included worsening of MG (1%, 5%, 17%), upper respiratory tract infection (12%, 8%, 11%), urinary tract infection (5%, 6%, 3%), nasopharyngitis (5%, 3%, 4%), headache (5%, 11%, 10%), rash (5%, 3%, 1%), injection site reaction (4%, 8%, 1%), diarrhea (3%, 14%, 7%), arthralgia (1%, 6%, 1%), pain in extremity (1%, 5%, 1%), cough (1%, 5%, 1%), and pruritus (0%, 5%, 0%). There were no deaths during the 24-week placebo-controlled portion of the trial but there was 1 death each in the cemdisiran and cemdi-poze arms in the extension period, due to pneumonia and septic shock, respectively, in patients who were on concomitant immuno-suppressive therapies.1

“The NIMBLE trial results underscore the potential for cemdisiran to offer a best-in-class profile for those suffering with myasthenia gravis, providing for robust efficacy with a convenient quarterly subcutaneous administration,” George D. Yancopoulos, MD, PhD, Board co-Chair, President and Chief Scientific Officer at Regeneron, added.1 “The potential for best-in-class efficacy with less than complete complement blockade with cemdisiran monotherapy may also provide for a more favorable safety profile. These exciting results highlight the transformative potential of our siRNA and genetic medicines pipeline to deliver paradigm-changing therapies for patients.”

References

1. Regeneron Announces Positive Results from Phase 3 Trial in Generalized Myasthenia Gravis. News release. Regeneron. August 26, 2025. https://www.globenewswire.com/news-release/2025/08/26/3139144/0/en/Regeneron-Announces-Positive-Results-from-Phase-3-Trial-in-Generalized-Myasthenia-Gravis.html

2. Novel Combination of Pozelimab and Cemdisiran (Poze-Cemdi) Achieved Greater Control of Intravascular Hemolysis in Patients with Paroxysmal Nocturnal Hemoglobinuria Compared to Ravulizumab. December 7, 2025. Accessed August 26, 2025. https://investor.regeneron.com/news-releases/news-release-details/novel-combination-pozelimab-and-cemdisiran-poze-cemdi-achieved