cemdisiran (ALN-CC5) / Alnylam, Regeneron - LARVOL DELTA

ACCESS-EXT: A Study in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) to Evaluate How Safe Long-term Treatment With Pozelimab + Cemdisiran Combination Therapy is and How Well it Works (clinicaltrials.gov) - P3 | N=202 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Trial completion date: Feb 2029 ➔ Oct 2028 | Trial primary completion date: Feb 2029 ➔ Oct 2028

Trial completion date • Trial primary completion date • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

Regeneron indicated that the FDA will review the New Drug Application (NDA) under Priority Review with a target action date in November 2026, following use of a Priority Review Voucher, and that a decision from the European Commission is anticipated in the second half of 2027. (Businesswire)

EMA approval • FDA approval • Myasthenia Gravis

SIENNA: A Study Investigating Subcutaneously Administered Pozelimab in Combination With Cemdisiran or Cemdisiran Alone in Adult Participants With Geographic Atrophy (clinicaltrials.gov) - P3 | N=975 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Trial completion date: May 2032 ➔ Apr 2033 | Trial primary completion date: Nov 2027 ➔ Jul 2028

Trial completion date • Trial primary completion date • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

A Study to Examine the Efficacy and Safety of Pozelimab and Cemdisiran Combination Therapy in Adult Patients With Symptomatic Generalized Myasthenia Gravis (clinicaltrials.gov) - P3; N=210; Not yet recruiting; Sponsor: Regeneron Pharmaceuticals

Clinical • Combination therapy • New P3 trial • CNS Disorders • Myasthenia Gravis

NIMBLE: A Study to Examine the Efficacy and Safety of Pozelimab and Cemdisiran Combination Therapy in Adult Patients With Symptomatic Generalized Myasthenia Gravis (clinicaltrials.gov) - P3 | N=235 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Trial completion date: May 2027 ➔ Mar 2028 | Trial primary completion date: Aug 2024 ➔ Aug 2025

Combination therapy • Trial completion date • Trial primary completion date • CNS Disorders • Myasthenia Gravis

A Study to Examine the Efficacy and Safety of Pozelimab and Cemdisiran Combination Therapy in Adult Patients With Symptomatic Generalized Myasthenia Gravis (clinicaltrials.gov) - P3 | N=210 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Not yet recruiting ➔ Recruiting | Trial primary completion date: Feb 2024 ➔ Aug 2024

Combination therapy • Enrollment open • Trial primary completion date • CNS Disorders • Myasthenia Gravis

NIMBLE: A Study to Test How Safe Pozelimab and Cemdisiran Combination Therapy and Cemdisiran Alone Are and How Well They Work in Adult Patients With Generalized Myasthenia Gravis (clinicaltrials.gov) - P3 | N=335 | Recruiting | Sponsor: Regeneron Pharmaceuticals | N=235 ➔ 335 | Trial completion date: Mar 2028 ➔ Mar 2029 | Trial primary completion date: May 2025 ➔ May 2026

Enrollment change • Monotherapy • Trial completion date • Trial primary completion date • CNS Disorders • Myasthenia Gravis

NIMBLE: A Study to Test How Safe Pozelimab and Cemdisiran Combination Therapy and Cemdisiran Alone Are and How Well They Work in Adult Patients With Generalized Myasthenia Gravis (clinicaltrials.gov) - P3 | N=235 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Trial primary completion date: Aug 2025 ➔ May 2025

Combination therapy • Monotherapy • Trial primary completion date • CNS Disorders • Myasthenia Gravis

NIMBLE: A Study to Test How Safe Pozelimab and Cemdisiran Combination Therapy and Cemdisiran Alone Are and How Well They Work in Adult Patients With Generalized Myasthenia Gravis (clinicaltrials.gov) - P3 | N=335 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Trial primary completion date: May 2026 ➔ Jul 2025

Monotherapy • Trial primary completion date • CNS Disorders • Myasthenia Gravis

NIMBLE: A Study to Test How Safe Pozelimab and Cemdisiran Combination Therapy and Cemdisiran Alone Are and How Well They Work in Adult Patients With Generalized Myasthenia Gravis (clinicaltrials.gov) - P3 | N=288 | Active, not recruiting | Sponsor: Regeneron Pharmaceuticals | Recruiting ➔ Active, not recruiting | Trial completion date: Mar 2029 ➔ Nov 2028

Enrollment closed • Monotherapy • Trial completion date • CNS Disorders • Myasthenia Gravis

Another complement inhibitor therapy for myasthenia gravis: Is it NIMBLE enough? (PubMed, Med) - "The phase 3 NIMBLE trial demonstrated the efficacy of cemdisiran, an siRNA inhibitor of hepatic C5 synthesis, in patients with myasthenia gravis, making it the first complement inhibitor in the disease to employ this novel mechanism of action. These results expand the growing therapeutic landscape that already includes three FDA-approved complement inhibitors for myasthenia gravis."

Journal • CNS Disorders • Myasthenia Gravis

An si-RNA‑Based Complement Pathway Inhibitor for gMG: Efficacy, Safety, and Impact on Quality of Life/MGC from the NIMBLE Trial (ICNMD 2026) - P3 | "Cemdisiran, both as monotherapy and in combination with pozelimab, significantly improves clinical signs and symptoms in people with gMG and was generally well-tolerated. Quarterly subcutaneous administration of cemdisiran provides effective symptom relief and enhanced quality of life, with partial complement inhibition."

Clinical • HEOR • CNS Disorders • Infectious Disease • Meningococcal Infections • Myasthenia Gravis • Pneumonia • Respiratory Diseases • Septic Shock

Efficacy and cumulative safety of cemdisiran in adults with generalised myasthenia gravis (gMG): results from the phase 3 NIMBLE trial (EAN 2026) - "The phase 3 NIMBLE trial evaluated subcutaneous cemdisiran (siRNA inhibiting hepatic C5 production) and subcutaneous pozelimab (monoclonal antibody targeting C5) as monotherapies or in combination in patients with gMG. Quarterly, subcutaneous cemdisiran was generally well-tolerated and achieved significant improvement in symptoms with partial complement inhibition among patients with gMG."

Clinical • P3 data • CNS Disorders • Infectious Disease • Meningococcal Infections • Myasthenia Gravis • Pneumonia • Respiratory Diseases • Septic Shock

Cemdisiran Regulatory Submissions Accepted for Review by FDA and EMA for the Treatment of Generalized Myasthenia Gravis (gMG) (GlobeNewswire) - "FDA accepted NDA under Priority Review with a target action date in November 2026; European Commission decision anticipated in the second half of 2027...The submissions are supported by data from the Phase 3 NIMBLE trial evaluating cemdisiran, dosed subcutaneously every 12 weeks, in adults with symptomatic gMG who may be receiving standard of care immunosuppressants based on the investigator’s discretion....A regulatory filing in Japan is also planned for early 2027."

EMA approval • FDA approval • FDA filing • Japan filing • Priority review • Myasthenia Gravis

COMPARISONS OF TERMINAL COMPLEMENT INHIBITION WITH POZELIMAB + CEMDISIRAN VERSUS RAVULIZUMAB IN PARTICIPANTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA: PHARMACODYNAMIC RESULTS FROM COHORT A (EHA 2026) - "Summary/Conclusion Combination therapy produced more rapid and durable effects across CH50 and AH50 versus ravulizumab in participants with PNH. These data indicate earlier onset and superior complement pathway control with the combination therapy compared to ravulizumab, supporting its potential to provide uninterrupted terminal complement activity suppression over 26 weeks."

PK/PD data • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Thrombosis

Comparative Network Meta-Analysis (NMA) of Sibeprenlimab Efficacy in the Treatment of Immunoglobulin A Nephropathy (IgAN) (NKF-SCM 2026) - "Treatments analyzed were: sibeprenlimab, atacicept, atrasentan, sparsentan, cemdisiran, TRF-budesonide, ravulizumab, and iptacopan. CONCLUSION Sibeprenlimab demonstrates clinically significant reductions in uPCR compared with other treatments, suggesting potential in IgAN. Updated NMA will be conducted when full Phase 3 results for sibeprenlimab are available."

Retrospective data • Glomerulonephritis • IgA Nephropathy • Renal Disease

A novel systemic approach to geographic atrophy with pozelimab in combination with cemdisiran or cemdisiran alone: The phase 3 SIENNA study design (ARVO 2026) - P3 | "Completion of enrollment in cohort A is expected in Q1 2026, and initial results are expected by the end of 2026. Conclusions SIENNA will provide important information on the efficacy, safety, and tolerability of a systemic approach for complete versus partial inhibition of C5 for GA treatment."

Combination therapy • P3 data • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Ophthalmology

A Study to Evaluate How Pozelimab + Cemdisiran Combination Therapy Works in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Whose Current Treatment is Not Working Efficiently (clinicaltrials.gov) - P3 | N=35 | Recruiting | Sponsor: Regeneron Pharmaceuticals

Trial initiation date • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

ACCESS-1: A Study to Evaluate How Safe Pozelimab + Cemdisiran Combination Therapy is and How Well it Works in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Who Have Not Recently Received or Have Not Received Complement Inhibitor Treatment (clinicaltrials.gov) - P3 | N=202 | Active, not recruiting | Sponsor: Regeneron Pharmaceuticals | Trial completion date: Jan 2027 ➔ Oct 2026 | Trial primary completion date: Jan 2027 ➔ Oct 2026

Trial completion date • Trial primary completion date • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

Rapid and Sustained Efficacy of Subcutaneously Administered Cemdisiran Without Complete Complement Blockade in Patients with Generalized Myasthenia Gravis (gMG): Primary Efficacy and Safety Results from the Phase Three NIMBLE Trial (AAN 2026) - P3 | "Objective:Report on phase 3 NIMBLE trial (NCT05070858) comparing subcutaneous cemdisiran or pozelimab plus cemdisiran with placebo in patients with gMG.Background:gMG is characterized by complement activation at the neuromuscular junction. Although both arms demonstrated rapid and sustained improvements versus placebo and were generally well‑tolerated in patients with gMG, quarterly SC dosing of cemdisiran achieved efficacious outcomes without complete complement blockage."

Clinical • CNS Disorders • Infectious Disease • Meningococcal Infections • Myasthenia Gravis • Pneumonia • Respiratory Diseases • Septic Shock • LRP4

Efficacy and safety of cemdisiran siRNA in myasthenia gravis (NIMBLE): a double-blind, randomised, placebo-controlled, phase 3 trial. (PubMed, Lancet) - P3 | "Cemdisiran monotherapy and combination therapy were effective in the treatment of generalised myasthenia gravis, and were generally well tolerated. Subcutaneous dosing of cemdisiran, administered every 3 months, could provide a convenient treatment approach for generalised myasthenia gravis."

Journal • P3 data • CNS Disorders • Infectious Disease • Meningococcal Infections • Myasthenia Gravis • Respiratory Diseases

ACCESS-1: A Study to Evaluate How Safe Pozelimab + Cemdisiran Combination Therapy is and How Well it Works in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Who Have Not Recently Received or Have Not Received Complement Inhibitor Treatment (clinicaltrials.gov) - P3 | N=190 | Active, not recruiting | Sponsor: Regeneron Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

R3918-PNH-2483: A Study to Evaluate how Pozelimab + Cemdisiran Combination Therapy Works in Adult Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) whose Current Treatment is not Working Efficiently (clinicaltrialsregister.eu) - P2/3 | N=8 | Not yet recruiting | Sponsor: Regeneron Pharmaceuticals Inc.

New P2/3 trial • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

Emerging Therapies in IgA Nephropathy: From A Proliferation-Inducing Ligand (APRIL) and B-cell Activating Factor (BAFF) Inhibitors to Precision Medicine. (PubMed, Cureus) - "This review synthesizes current evidence on evolving treatments, with a focus on A Proliferation-Inducing Ligand (APRIL) and B-cell Activating Factor (BAFF) (e.g., sibeprenlimab, atacicept, povetacicept, telitacicept), complement pathway modulators (e.g., iptacopan, cemdisiran, ravulizumab), and novel agents such as felzartamab and sparsentan. It also explores precision medicine strategies, including biomarker-guided therapy, individualized risk stratification, and combination regimens. Supported by high-quality recent clinical trial data and the latest kidney disease outcome guidelines, these innovations represent a paradigm shift toward personalized, disease-modifying treatment in IgAN, offering a new horizon for improved renal outcomes and long-term disease control."

Journal • Review • Chronic Kidney Disease • Glomerulonephritis • IgA Nephropathy • Nephrology • Renal Disease

A Study to Evaluate How Pozelimab + Cemdisiran Combination Therapy Works in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Whose Current Treatment is Not Working Efficiently (clinicaltrials.gov) - P3 | N=35 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases