Cemdisiran monotherapy, dosed subcutaneously every three months, met the primary and key secondary endpoints, showing a 2.3-point placebo-adjusted improvement in Myasthenia Gravis Activities of Daily Living (MG-ADL) total score
U.S. regulatory submission for cemdisiran monotherapy is planned for the first quarter of 2026, pending discussions with the FDA
TARRYTOWN, N.Y., Aug. 26, 2025 (GLOBE NEWSWIRE) -- Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced that the primary and key secondary endpoints were met in the Phase 3 NIMBLE trial assessing investigational cemdisiran monotherapy in adults with generalized myasthenia gravis (gMG). Cemdisiran is an siRNA that reduces circulating levels of complement factor 5 (C5) and, as monotherapy in this trial, was associated with an average of 74% inhibition of complement activity. The trial also assessed a combination of cemdisiran and pozelimab, a C5 antibody; this combination (“cemdi-poze”), which resulted in nearly 99% inhibition of complement activity, also met the primary and key secondary endpoints, though cemdisiran monotherapy was numerically better across these endpoints.
“Our pipeline approach to treating complement-mediated diseases allows us to tailor treatment to the underlying disease biology,” said L. Andres Sirulnik, M.D., Ph.D., Senior Vice President and Hematology Clinical Development Unit Head at Regeneron. “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. We have previously released data from the lead-in portion of our PNH Phase 3 trial, supporting the potential for the cemdi-poze combination to deliver best-in-class efficacy in PNH. 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.”
“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,” said George D. Yancopoulos, M.D., Ph.D., Board co-Chair, President and Chief Scientific Officer at Regeneron. “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.”
The NIMBLE trial evaluated adults with symptomatic gMG who have antibodies to the acetylcholine receptor (anti-AChR) and may be receiving standard of care immunosuppressants based on the investigator’s discretion. Patients were randomized to receive subcutaneous administrations of: cemdisiran (600 mg) every 12 weeks, cemdi-poze (cemdisiran 200 mg and pozelimab 200 mg) every 4 weeks, or placebo every 4 weeks. 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 that measures daily functions impacted by gMG, such as talking, eating, breathing, vision and mobility. The key secondary endpoint assessed 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.
Historical clinical trial data report that currently approved C5 inhibitor therapies have shown a placebo-adjusted treatment difference in MG-ADL total scores ranging from -1.6 to -2.1 at 12 to 26 weeks.
Both cemdisiran and cemdi-poze demonstrated improvements in activities of daily functioning at week 24, with cemdisiran showing numerically better results across all gMG-specific outcomes. In the MG-ADL and QMG, greater reductions in total scores indicate greater improvement in disease symptoms and better treatment effect.
†Means and relative risks were adjusted per the amount immunosuppressant treatment and the Myasthenia Gravis Foundation of America Clinical Classification determined at screening. Means were also adjusted for baseline MG-ADL or QMG score.
There were no meningococcal infections in any patient. There were no 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 (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. During the extension period, one death due to pneumonia occurred in the cemdisiran arm, and one death due to septic shock occurred in the combination arm; both deaths occurred in patients who were on concomitant immuno-suppressive therapies.
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.
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.
About Myasthenia Gravis (MG)
MG is a rare and chronic autoimmune disease where abnormal antibodies activate the complement system including C5, disrupting communication between nerves and muscles that results in debilitating and potentially life-threatening muscle weakness. In the U.S., the disease impacts approximately 85,000 people. Initial manifestations are usually ocular, but approximately 85% of MG patients experience additional advancements to the disease manifestations, which is known as generalized myasthenia gravis (gMG). For these patients, the disease affects muscles throughout the body, resulting in extreme fatigue and difficulties with facial expression, speech, swallowing and mobility. Treatment-related challenges – which include frequent hospital visits, inconsistent symptom control, and lack of durable treatment effects – can further affect quality of life and long-term disease management.
About the Complement Factor 5 (C5) Clinical Program
NIMBLE is a randomized, double-blind, placebo-controlled trial evaluating cemdisiran and cemdi-poze in patients with gMG who have antibodies for AChR. The primary endpoint assessed changes in the MG-ADL total score from baseline to week 24. The MG-ADL scale is an eight-question patient-reported tool that measures how gMG affects aspects of daily life and provides a total score ranging from 0 to 24. The key secondary endpoint was the change from baseline in QMG total score at week 24. The QMG is a physician-administered 13-item standardized assessment evaluating muscle function that provides a total score ranging from 0 to 39. In both MG-ADL and QMG, a higher total score indicates greater disease severity, and a larger reduction in total score indicates greater improvement in disease symptoms and better treatment effect.
Cemdisiran and pozelimab are also being evaluated in separate Phase 3 trials as both monotherapy and combination therapy for additional complement-mediated disorders, including PNH and geographic atrophy secondary to age-related macular degeneration. For more information, visit the Regeneron clinical trials website, or contact clinicaltrials@regeneron.com or +1 844-734-6643.
Cemdisiran as a monotherapy and in combination with pozelimab was being developed under an initial agreement with Alnylam Pharmaceuticals, Inc. In June 2024, Regeneron and Alnylam entered into an amended and restated C5 License Agreement, which granted Regeneron a worldwide license to cemdisiran as a monotherapy in addition to a license to cemdisiran in combination with C5 antibodies. Regeneron is solely responsible for development, manufacturing, and commercialization of cemdisiran as a monotherapy and in combination with C5 antibodies. For cemdisiran as a monotherapy, Alnylam is entitled to receive certain regulatory milestone payments as well as tiered, double-digit royalties (up to 15%) on calendar-year net sales. If cemdisiran is used as part of a combination product, Alnylam is entitled to receive a flat, low double-digit royalty on calendar-year net sales as well as commercial milestones of up to $325.0 million.
About Regeneron's VelocImmune® Technology
Regeneron's VelocImmune technology utilizes a proprietary genetically engineered mouse platform endowed with a genetically humanized immune system to produce optimized fully human antibodies. When Regeneron's co-Founder, President and Chief Scientific Officer George D. Yancopoulos was a graduate student with his mentor Frederick W. Alt in 1985, they were the first to envision making such a genetically humanized mouse, and Regeneron has spent decades inventing and developing VelocImmune and related VelociSuite® technologies. Dr. Yancopoulos and his team have used VelocImmune technology to create a substantial proportion of all original, FDA-approved or authorized fully human monoclonal antibodies. This includes REGEN-COV® (casirivimab and imdevimab), Dupixent® (dupilumab), Libtayo® (cemiplimab-rwlc), Praluent® (alirocumab), Kevzara® (sarilumab), Evkeeza® (evinacumab-dgnb), Inmazeb® (atoltivimab, maftivimab and odesivimab-ebgn) and Veopoz® (pozelimab).
About Regeneron
Regeneron (NASDAQ: REGN) is a leading biotechnology company that invents, develops and commercializes life-transforming medicines for people with serious diseases. Founded and led by physician-scientists, our unique ability to repeatedly and consistently translate science into medicine has led to numerous approved treatments and product candidates in development, most of which were homegrown in our laboratories. Our medicines and pipeline are designed to help patients with eye diseases, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, neurological diseases, hematologic conditions, infectious diseases, and rare diseases.
Regeneron pushes the boundaries of scientific discovery and accelerates drug development using our proprietary technologies, such as VelociSuite, which produces optimized fully human antibodies and new classes of bispecific antibodies. We are shaping the next frontier of medicine with data-powered insights from the Regeneron Genetics Center® and pioneering genetic medicine platforms, enabling us to identify innovative targets and complementary approaches to potentially treat or cure diseases.