Regeneron's Cemdisiran Shows Promising Results in Rare Autoimmune Muscle Disorder Trial

Regeneron Pharmaceuticals has reported positive Phase 3 trial data for cemdisiran monotherapy in adults with generalized myasthenia gravis. The trial met primary and key secondary endpoints, with cemdisiran reducing circulating complement factor 5 levels by 74%. The combination of cemdisiran and pozelimab resulted in nearly 99% inhibition of complement activity, also meeting endpoints. Regeneron plans to submit a U.S. regulatory application for cemdisiran in Q1 2026.

Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) has announced positive results from its Phase 3 NIMBLE trial evaluating cemdisiran monotherapy in adults with generalized myasthenia gravis (gMG). The trial met its primary and key secondary endpoints, demonstrating the drug's efficacy in reducing circulating complement factor 5 (C5) levels by an average of 74% [1].

The primary endpoint assessed total score changes from baseline to week 24 in the Myasthenia Gravis Activities of Daily Living (MG-ADL) total score, a patient-reported questionnaire measuring daily functions impacted by gMG. The key secondary endpoint assessed changes in the Quantitative Myasthenia Gravis (QMG) total score, a physician-administered assessment evaluating vision, speaking/swallowing, breathing, and limb function. Both endpoints were met, with cemdisiran showing numerically better results across all gMG-specific outcomes compared to the combination of cemdisiran and pozelimab, which resulted in nearly 99% inhibition of complement activity [1].

The trial evaluated adults with symptomatic gMG who have antibodies to the acetylcholine receptor (anti-AChR) and may be receiving standard of care immunosuppressants. Patients were randomized to receive subcutaneous administrations of cemdisiran (600 mg) every 12 weeks, the combination of cemdisiran and pozelimab (cemdi-poze) every 4 weeks, or placebo every 4 weeks. The primary endpoint showed a placebo-adjusted treatment difference of -2.30 (p=0.0005) for cemdisiran, indicating a significant improvement in activities of daily functioning [1].

Regeneron plans to submit a U.S. regulatory application for cemdisiran in the first quarter of 2026, pending discussions with the FDA [1]. The potential use of cemdisiran and/or pozelimab for the treatment of gMG is investigational and has not been approved by any regulatory authority. In the U.S., pozelimab monotherapy is approved as Veopoz® (pozelimab-bbfg) for adult and pediatric patients 1 year of age and older with CHAPLE disease, also known as CD55-deficient protein-losing enteropathy, which includes a Boxed Warning for life-threatening and fatal meningococcal infections [1].

Myasthenia Gravis (MG) is a rare and chronic autoimmune disease affecting approximately 85,000 people in the U.S. Initial manifestations are usually ocular, but approximately 85% of MG patients experience additional advancements to the disease manifestations, known as generalized myasthenia gravis (gMG). Treatment-related challenges, including frequent hospital visits, inconsistent symptom control, and lack of durable treatment effects, can further affect quality of life and long-term disease management [1].

Regeneron's pipeline approach to treating complement-mediated diseases allows for tailoring treatment to the underlying disease biology. The results of the NIMBLE trial confirm that in myasthenia gravis, 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 [1]. The company is also investigating systemic administration of both cemdisiran monotherapy and the cemdi-poze combination in its Phase 3 program for geographic atrophy secondary to age-related macular degeneration [1].

The trial showed no meningococcal infections or treatment discontinuations due to adverse events through week 24 in the cemdisiran arm. Across all arms, treatment-emergent adverse events (TEAEs) occurred in 69% of patients treated with cemdisiran, 81% with cemdi-poze, and 77% with placebo. Serious TEAEs occurred in 3% of patients treated with cemdisiran, 9% with cemdi-poze, and 14% with placebo. The most common TEAEs observed in ≥5% of patients receiving cemdisiran, cemdi-poze, or placebo were worsening of MG, upper respiratory tract infection, urinary tract infection, nasopharyngitis, headache, rash, injection site reaction, diarrhea, arthralgia, pain in extremity, cough, and pruritus [1].

Detailed results from the NIMBLE trial will be presented at an upcoming medical meeting. The U.S. regulatory application for cemdisiran is planned for the first quarter of 2026, pending discussions with the FDA [1].

References:
[1] https://newsroom.regeneron.com/news-releases/news-release-details/regeneron-announces-positive-results-phase-3-trial-generalized