Povetacicept

Not approved by the FDA, EMA or any other regulator; administered only in clinical trials. United States: povetacicept holds FDA Breakthrough Therapy Designation for IgA nephropathy, and on June 1, 2026 the FDA accepted a Biologics License Application (BLA) for accelerated approval in IgAN (rolling review) with a PDUFA target action date of November 30, 2026. Accelerated approval, if granted, would rest on the reduction in urine protein-to-creatinine ratio (UPCR) as a surrogate endpoint, with confirmatory kidney-function (eGFR) data expected from the ongoing Phase 3 RAINIER trial.

Efgartigimod (efgartigimod alfa, brand names Vyvgart intravenous and Vyvgart Hytrulo subcutaneous) is a first-in-class antagonist of the neonatal Fc receptor (FcRn) developed by argenx as ARGX-113. It is not a small synthetic peptide but an engineered fragment of the human immunoglobulin G1 (IgG1) antibody - specifically the Fc portion that normally binds FcRn - modified with argenx's ABDEG technology to bind FcRn with much higher affinity than natural IgG at both neutral and acidic pH. FcRn is the salvage receptor that rescues circulating IgG from lysosomal degradation and recycles it back into the blood, giving antibodies their long half-life. By outcompeting endogenous IgG for FcRn, efgartigimod blocks that recycling and drives rapid clearance of IgG - including the pathogenic autoantibodies that cause many autoimmune diseases - typically lowering total IgG by roughly 60-70% within weeks, without reducing IgM, IgA, or albumin. It was the first FcRn blocker ever approved: FDA-approved in December 2021 (Vyvgart IV) for acetylcholine-receptor-antibody-positive generalized myasthenia gravis (gMG) on the strength of the Phase 3 ADAPT trial, followed by a subcutaneous co-formulation with recombinant hyaluronidase (Vyvgart Hytrulo) for gMG in 2023 and for chronic inflammatory demyelinating polyneuropathy (CIDP) in 2024. In May 2026 the FDA expanded the gMG label to all serotypes - including AChR-antibody-negative (seronegative) patients - based on the Phase 3 ADAPT SERON trial, making efgartigimod the first and only therapy approved across every gMG antibody subtype. It is being studied in a broad set of other IgG-driven autoimmune diseases, including primary immune thrombocytopenia, myositis, Sjogren's disease, bullous pemphigoid, and lupus nephritis.

Nipocalimab (brand name Imaavy, development code M281) is a fully human, aglycosylated, 'effectorless' IgG1 monoclonal antibody that blocks the neonatal Fc receptor (FcRn), developed by Johnson & Johnson (Janssen). Like efgartigimod it lowers circulating immunoglobulin G (IgG) - including the pathogenic autoantibodies that drive many autoimmune diseases - by occupying FcRn and preventing it from recycling IgG back into the blood, so unrescued IgG is routed to the lysosome and degraded, typically cutting total IgG by roughly 65-75% while sparing IgM, IgA, complement, and albumin. Unlike efgartigimod's engineered Fc fragment, nipocalimab is a full-length monoclonal antibody engineered to be aglycosylated and effectorless (it does not trigger ADCC or complement-dependent cytotoxicity), and it is dosed as a maintenance intravenous infusion for continuous IgG suppression rather than in short cycles. The FDA approved Imaavy on April 30, 2025 for generalized myasthenia gravis (gMG) in anti-AChR-antibody-positive and anti-MuSK-antibody-positive patients aged 12 and older - making it the first FcRn blocker approved for adolescents and the first to explicitly cover MuSK-positive disease - on the strength of the Phase 3 Vivacity-MG3 trial. It has since generated positive data across a striking breadth of IgG-mediated conditions: Sjogren's disease (Phase 2 DAHLIAS), rheumatoid arthritis, warm autoimmune hemolytic anemia (wAIHA), and - uniquely among FcRn blockers - maternal-fetal alloimmune disease, where it is being developed to treat hemolytic disease of the fetus and newborn (HDFN) by crossing the placenta to protect the fetus. In April 2026 the FDA granted Priority Review to nipocalimab for wAIHA, positioning it as a potential first approved therapy for that condition.

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.

Rozanolixizumab (brand name Rystiggo, development code UCB7665) is a humanized IgG4 monoclonal antibody that blocks the neonatal Fc receptor (FcRn), developed by UCB. Like efgartigimod and nipocalimab it lowers circulating immunoglobulin G (IgG) - including the pathogenic autoantibodies that drive many autoimmune diseases - by binding FcRn and preventing it from recycling IgG back into the blood, so unrescued IgG is routed to the lysosome and degraded, typically cutting total IgG by roughly 70-80% while sparing IgM, IgA, complement, and albumin. Unlike efgartigimod's engineered Fc fragment, rozanolixizumab is a full-length humanized antibody, and unlike nipocalimab's intravenous infusion it is given as a rapid subcutaneous infusion (including via an on-body delivery device), typically in weekly cycles that are repeated based on clinical response rather than continuously. The FDA approved Rystiggo on June 27, 2023 for generalized myasthenia gravis (gMG) in adults who are anti-acetylcholine-receptor (AChR) antibody-positive or anti-muscle-specific-tyrosine-kinase (MuSK) antibody-positive - making it the first therapy ever approved to treat both of those gMG subtypes - on the strength of the Phase 3 MycarinG trial. It has since been studied across other IgG-mediated diseases, including chronic inflammatory demyelinating polyneuropathy (CIDP), where it did not show meaningful benefit and was not advanced to Phase 3, and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), primary immune thrombocytopenia (ITP), and other autoantibody conditions where development continues. The European Medicines Agency approved rozanolixizumab in January 2024 and the UK MHRA in March 2024.

Sotatercept (Winrevair, sotatercept-csrk) is Merck's first-in-class activin signaling inhibitor - a recombinant ActRIIA-Fc fusion protein that acts as a ligand trap for activin A, activin B, GDF-8 (myostatin) and GDF-11. It is FDA-approved for adults with pulmonary arterial hypertension (PAH), where it improved 6-minute walk distance by 40.8 meters in the Phase 3 STELLAR trial and, in the Phase 3 ZENITH trial in high-risk patients, cut the composite risk of death, lung transplantation and PAH hospitalization by 76%. An expanded U.S. label reflecting ZENITH was approved on October 27, 2025.

A self-administered, once-daily subcutaneous macrocyclic peptide that inhibits complement component 5 (C5), FDA- and EMA-approved for anti-AChR-positive generalized myasthenia gravis.

Sibeprenlimab (brand name VOYXACT; nonproprietary name sibeprenlimab-szsi; development code VIS649) is a humanized monoclonal antibody that binds and neutralizes APRIL (a proliferation-inducing ligand), a cytokine that drives the abnormal, antibody-producing B cells behind IgA nephropathy. By soaking up circulating APRIL with very high affinity, it lowers production of galactose-deficient IgA1 (Gd-IgA1) - the mis-glycosylated antibody whose immune complexes deposit in the kidney and cause the proteinuria and progressive damage of IgA nephropathy (IgAN). Given as a fixed 400 mg subcutaneous injection once every 4 weeks from a single-dose prefilled syringe, sibeprenlimab is designed for at-home self-administration. Originated by Visterra (acquired by Otsuka Pharmaceutical in 2018), it advanced through the Phase 2 ENVISION trial and the pivotal Phase 3 VISIONARY trial - the largest Phase 3 study conducted in IgAN - where it produced a roughly 50-54% placebo-adjusted reduction in proteinuria and signs of preserved kidney function (eGFR). On the strength of those data and an FDA Breakthrough Therapy Designation, the U.S. FDA granted VOYXACT accelerated approval in November 2025 to reduce proteinuria in adults with primary IgAN at risk of disease progression, and Otsuka began a rolling supplemental filing in 2026 seeking traditional approval on longer-term kidney-function data. Sibeprenlimab is a prescription biologic administered under medical care; it is not a supplement, nootropic, or research chemical.

Felzartamab (development codes MOR202/MOR03087, and TJ202 in Greater China) is an investigational fully human IgG1 monoclonal antibody that targets CD38, a protein carried at high density on the antibody-producing plasma cells and plasmablasts of the immune system. Rather than blocking a single circulating antibody or downstream mediator, felzartamab depletes the very cells that manufacture pathogenic (disease-causing) antibodies, with the logic that shutting down the factory stops the harmful antibodies at their source. CD38 antibodies are an established drug class in cancer (daratumumab and isatuximab are approved for multiple myeloma), and felzartamab is being repurposed to switch off the autoantibody-driven immune attack behind several serious kidney diseases. It is given as an intravenous infusion in defined treatment courses (for example, a roughly five- to nine-dose regimen) rather than indefinitely. Felzartamab has become one of the most closely watched agents in nephrology because it is advancing through three separate Phase 3 programs in rare, antibody-mediated kidney diseases: IgA nephropathy (IgAN), primary membranous nephropathy (PMN), and late antibody-mediated rejection (AMR) of a transplanted kidney. It originated at MorphoSys AG, was licensed to Human Immunology Biosciences (HI-Bio), which Biogen acquired in 2024, and Biogen consolidated the Greater China rights from TJ Biopharma in 2026. It holds FDA Breakthrough Therapy designation in primary membranous nephropathy. Felzartamab is an investigational prescription biologic administered under medical supervision; it is not approved for kidney disease, and it is not a supplement, nootropic or research chemical.

Frexalimab (SAR441344) is an investigational second-generation, fully human monoclonal antibody from Sanofi that blocks CD40 ligand (CD40L, also called CD154), a costimulatory 'second signal' that helps activate B cells, T cells and antigen-presenting cells and drives adaptive autoimmunity. Rather than depleting immune cells, frexalimab interrupts the CD40-CD40L checkpoint upstream - a mechanism related to but distinct from the OX40-OX40L blockade of amlitelimab. Its lead indication is relapsing multiple sclerosis (RMS), with a second program in nonrelapsing secondary progressive MS (nrSPMS). In the Phase 2 relapsing-MS trial (NCT04879628, published in the New England Journal of Medicine in 2024), frexalimab cut the number of new gadolinium-enhancing brain lesions at week 12 by 89% (higher-dose IV arm) and 79% (lower-dose subcutaneous arm) versus placebo, and open-label extensions out to two and three years show that disease control and reductions in neurofilament light have been sustained. Crucially, frexalimab is engineered so its Fc region does not activate platelets, which is designed to avoid the thromboembolic complications that halted first-generation anti-CD40L antibodies decades ago. It is now in the Phase 3 FREXALT (relapsing MS, versus teriflunomide) and FREVIVA (nrSPMS, versus placebo) trials, with additional Phase 2 programs in type 1 diabetes (FABULINUS) and systemic lupus erythematosus; a Sjogren's syndrome study was discontinued in 2024 after it fell short on efficacy. Frexalimab is investigational and not approved by any regulator.

Atacicept (brand name Trutakna) is a recombinant soluble TACI-Fc fusion protein and the first dual BAFF/APRIL inhibitor approved for IgA nephropathy (IgAN). It fuses the extracellular ligand-binding domain of the TACI receptor to the Fc region of human IgG1, letting it soak up two B-cell survival cytokines at once - BAFF (B-cell activating factor) and APRIL (a proliferation-inducing ligand). By starving autoreactive B cells and plasma cells of both signals, atacicept lowers production of galactose-deficient IgA1 (Gd-IgA1), the abnormal antibody that drives immune-complex deposition and kidney injury in IgAN. It is given as a 150 mg once-weekly subcutaneous self-injection with an autoinjector at home. On July 7, 2026 the FDA granted atacicept accelerated approval (as Trutakna) to reduce proteinuria in adults with primary IgAN at risk of progression - the first and only BAFF-and-APRIL inhibitor cleared for the disease - based on the Phase 3 ORIGIN 3 trial (NCT04716231, 431 adults), in which it cut urine protein (UPCR) 46% from baseline and 42% versus placebo at week 36 (p<0.0001), reduced Gd-IgA1 by 68%, resolved hematuria in 81% of those with baseline blood in the urine, and produced serious adverse events in only 0.5% of patients (versus 5% on placebo). Originated at ZymoGenetics and developed by Merck KGaA (Merck Serono) before being out-licensed to Vera Therapeutics, atacicept sits alongside the anti-APRIL antibody sibeprenlimab and the engineered dual BAFF/APRIL inhibitor povetacicept in the fast-moving IgAN pipeline.