Regeneron outlines multi‑indication C5 strategy

Regeneron Pharmaceuticals (REGN) has outlined a unified C5 complement inhibition strategy built around cemdisiran, an siRNA targeting C5, and pozelimab, a C5‑directed antibody already approved for an ultra‑rare disease. The plan was presented at an investor roundtable focused on paroxysmal nocturnal hemoglobinuria (PNH), generalized myasthenia gravis (gMG) and geographic atrophy (GA).

Board co‑chair, president and chief scientific officer George Yancopoulos said the approach is the first time an antibody and an siRNA have been combined to inhibit the same pathway. Cemdisiran lowers hepatic C5 production while pozelimab neutralizes residual circulating C5, enabling near‑complete blockade in combination or more moderate inhibition when used alone.

Executives described a “match the biology” strategy, selecting cemdisiran, pozelimab or their combination to tune the depth of complement inhibition by disease. The company highlighted this C5 effort as one of five late‑stage programs it believes could deliver meaningful advances over the next several years.

Ryan Crowe, senior vice president of investor relations, pointed to several upcoming milestones. Registrational PNH data from the ACCESS program are expected in the fourth quarter, following completion of enrollment in Cohort B. Initial phase III lead‑in results from the SIENA GA trial are anticipated late this year.

Crowe also noted that an NDA for cemdisiran in gMG has been submitted to the U.S. Food and Drug Administration using a priority review voucher, with an FDA decision expected in the fourth quarter. Regeneron is preparing for a potential U.S. launch of cemdisiran in gMG later in 2026.

Andres Sirulnik, head of hematology clinical development, described PNH as driven by uncontrolled C5 activation, with remaining unmet need despite current therapies. The phase III ACCESS I program compares cemdisiran plus pozelimab to ravulizumab in Cohort A and to eculizumab in registrational Cohort B.

Exploratory 26‑week Cohort A data previously showed nearly all patients on the combination achieving LDH control (≤1.5×ULN), with 96% maintaining hemolysis control, versus 80% on ravulizumab. In an extension phase, patients who switched from ravulizumab to the combination demonstrated improved LDH control, including prior non‑responders.

Regeneron has also started a first‑in‑human study of an siRNA targeting complement factor B, initially for PNH patients who remain anemic due to extravascular hemolysis despite optimal C5 therapy, with potential broader applications.

Umesh Chaudhari, global C5 program head, said gMG is driven by complement‑mediated damage at the neuromuscular junction and positioned cemdisiran as a way to provide sustained disease control with lower treatment burden. In the phase III NIMBLE trial, acetylcholine receptor‑positive patients received subcutaneous cemdisiran every 12 weeks.

Cemdisiran monotherapy met the primary endpoint of change in MG‑ADL at week 24 and all key secondary endpoints, including a 2.3‑point placebo‑adjusted MG‑ADL improvement and a 2.8‑point QMG improvement. Efficacy was seen by week two and remained consistent between doses.

A combination arm with pozelimab also met endpoints but did not provide additional benefit versus cemdisiran alone, supporting Regeneron’s view that gMG may not require complete complement blockade. Cemdisiran was generally well tolerated through 24 weeks, with no serious or meningococcal infections and no treatment discontinuations in the double‑blind period.

Sirulnik described GA as an irreversible form of dry age‑related macular degeneration where existing intravitreal complement inhibitors carry ocular safety concerns and frequent injection burden. Regeneron’s phase III SIENA trial is testing systemic C5 inhibition in roughly 975 GA patients using a seamless two‑cohort structure.

Cohort A of SIENA is fully enrolled, with interim data expected in the fourth quarter of 2026. This readout is intended as a decision point to determine whether cemdisiran monotherapy, pozelimab, or combination therapy is needed, rather than as a standalone regulatory submission.

Yancopoulos said the GA program is powered to detect potential functional benefit, and argued that systemic subcutaneous dosing could be attractive for bilateral disease and patients also receiving anti‑VEGF therapy. Regeneron is additionally developing an intravitreal pozelimab formulation, citing potential durability and co‑formulation with anti‑VEGF agents.

Soma Gupta, vice president of commercial new products, said Regeneron sees the C5 program as a multi‑indication, multi‑billion‑dollar opportunity across gMG, PNH and GA. She estimated that these three markets together generate about $9 billion in annual worldwide sales.

Regeneron holds full responsibility for development, manufacturing and commercialization of cemdisiran and the combination, while paying modest royalties on net sales to Alnylam. Gupta identified gMG as the first and largest near‑term commercial opportunity.

Advanced therapy penetration in gMG is estimated at about 15% and is expected to trend toward 40% over time. Regeneron plans to position cemdisiran as a differentiated, quarterly subcutaneous targeted therapy, with anticipated use in both switch and new‑start patients and a transition from in‑office dosing to potential self‑administration, subject to regulators.

Yancopoulos emphasized that the C5 initiative is not a single‑asset program but a tunable platform across indications. Management characterized the franchise as an underappreciated long‑term growth opportunity, anchored by upcoming pivotal data and planned launches in multiple diseases.