Danicopan

A PEGylated cyclic-peptide inhibitor of complement component 3 (C3) built from two compstatin (Cp05) peptide domains bridged by a 40-kDa PEG chain; marketed as Empaveli/Aspaveli (subcutaneous, for paroxysmal nocturnal hemoglobinuria and, since July 2025, C3 glomerulopathy and primary IC-MPGN) and Syfovre (intravitreal, for geographic atrophy in age-related macular degeneration). It is one of the few complement-targeting therapeutic peptides to reach the market.

Cemdisiran is an investigational GalNAc-conjugated small interfering RNA (siRNA) that silences the gene for complement component 5 (C5) in the liver, durably lowering circulating C5. It is being developed by Regeneron (under a license from Alnylam, which originated the molecule as ALN-CC5) as a subcutaneous, once-every-12-weeks treatment for adults with anti-acetylcholine-receptor (AChR) antibody-positive generalized myasthenia gravis (gMG) - an autoimmune disease in which antibodies and complement attack the neuromuscular junction, so that activation of C5 and formation of the membrane attack complex destroy the acetylcholine receptors that make muscles contract, causing fluctuating, fatigable weakness. By knocking down C5 production rather than blocking the circulating protein with an antibody or peptide, cemdisiran offers quarterly dosing instead of the weekly-to-monthly injections of existing complement inhibitors. The pivotal Phase 3 NIMBLE trial (NCT05070858) - a randomized, double-blind, placebo-controlled study of about 284 adults with gMG, published in The Lancet in 2026 and presented at the American Academy of Neurology annual meeting - compared cemdisiran 600 mg given subcutaneously every 12 weeks against placebo and against a pozelimab-plus-cemdisiran combination. In the cemdisiran monotherapy arm the mean MG-ADL (Myasthenia Gravis Activities of Daily Living) score improved by 4.5 points from baseline at week 24 versus 2.2 points on placebo, a placebo-adjusted improvement of 2.3 points (p<0.001), with 76.6% of cemdisiran patients achieving at least a 3-point MG-ADL improvement versus 44.1% on placebo; the QMG (Quantitative Myasthenia Gravis) score improved by 4.2 versus 1.5 points, a placebo-adjusted 2.8 points (p=0.002), and benefits appeared within two weeks. No serious infections, meningococcal infections or deaths occurred during the double-blind treatment period, and there were no discontinuations for adverse events through week 24. Regeneron submitted a regulatory application in the first quarter of 2026; the FDA accepted it under Priority Review with a target action date in November 2026, and a European application is under review with a decision expected in the second half of 2027. If approved, cemdisiran would be the first RNA-interference (siRNA) therapy for generalized myasthenia gravis. It is investigational and not yet approved for this use anywhere.

Regeneron's fully human anti-C5 monoclonal antibody (Veopoz) — the first approved treatment for CHAPLE disease and the antibody half of the cemdisiran combination for complement-driven disease.

Chugai/Roche's humanized recycling anti-C5 monoclonal antibody (Piasky) — FDA-approved for paroxysmal nocturnal hemoglobinuria as a low-volume, once-monthly subcutaneous injection patients can give themselves.

Novartis's Fabhalta (iptacopan, development code LNP023) - the first approved oral, first-in-class small-molecule factor B inhibitor that selectively blocks the alternative complement pathway at its proximal amplification loop; taken as a 200 mg capsule twice daily, it is FDA-approved for paroxysmal nocturnal hemoglobinuria (PNH), for primary IgA nephropathy (IgAN), and as the first-ever treatment for C3 glomerulopathy (C3G), and in July 2026 it became the first and only complement inhibitor to win traditional FDA approval for slowing kidney function decline in IgAN, cutting the annual rate of eGFR loss by about 48% versus placebo in the Phase 3 APPLAUSE-IgAN trial.

Avacopan (brand Tavneos, development code CCX168) is a first-in-class, oral, small-molecule antagonist of the complement C5a receptor (C5aR1, also called CD88) from ChemoCentryx (now part of Amgen). Taken as 30 mg (three 10 mg capsules) twice daily with food, it blocks C5a from activating neutrophils and is FDA-approved as an adjunctive treatment for adults with severe active ANCA-associated vasculitis (granulomatosis with polyangiitis, GPA, and microscopic polyangiitis, MPA) alongside standard therapy (rituximab or cyclophosphamide). It is designed to let patients taper off high-dose glucocorticoids, not to replace immunosuppression.