Frexalimab

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.

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.

Povetacicept (development code ALPN-303) is an investigational, once-monthly, subcutaneously injected recombinant fusion protein that simultaneously blocks two B-cell survival signals - BAFF (B-cell activating factor) and APRIL (a proliferation-inducing ligand). It is built from an engineered ('variant') form of the natural TACI receptor's extracellular domain fused to an antibody (IgG) Fc region, so it acts as a high-affinity decoy that soaks up both BAFF and APRIL before they can reach their receptors on B cells and plasma cells. Because BAFF and APRIL drive the maturation and antibody production of the immune cells behind many autoantibody- and immune-complex-mediated diseases, povetacicept is being developed for B-cell-driven autoimmune conditions - most prominently IgA nephropathy (IgAN), where APRIL fuels the production of the galactose-deficient IgA1 that damages the kidney. Originated by Alpine Immune Sciences (acquired by Vertex Pharmaceuticals in 2024), povetacicept has received FDA Breakthrough Therapy Designation for IgAN; in March 2026 the Phase 3 RAINIER trial reported a positive prespecified Week 36 interim analysis (a ~52% reduction in urine protein-to-creatinine ratio from baseline and a ~50% reduction versus placebo), and in June 2026 the FDA accepted a Biologics License Application for accelerated approval with a target action date of November 30, 2026. Povetacicept is an experimental biologic given only in clinical trials; it is not a supplement, nootropic, or research chemical.

Amlitelimab (SAR445229, formerly KY1005) is a fully human, non-T-cell-depleting monoclonal antibody from Sanofi that blocks OX40 ligand (OX40L), a costimulatory signal that drives and sustains T-cell-mediated inflammation. Rather than neutralizing a single cytokine like IL-4/IL-13 (dupilumab) or IL-5 (depemokimab), amlitelimab acts upstream at the OX40-OX40L checkpoint to dampen a broad, memory-driven inflammatory program without depleting T cells. Its lead (anchor) indication is moderate-to-severe atopic dermatitis in people aged 12 and older, where a distinctive feature is very infrequent dosing: after a loading dose it is given subcutaneously as little as four times a year (every 12 weeks). In the Phase 3 program - COAST 1, COAST 2 and SHORE - amlitelimab met its primary endpoints with EASI-75 and vIGA-AD 0/1 responses that increased over time, though COAST 2's absolute response rates were more modest and some observers called that readout mixed. Amlitelimab is investigational and not yet approved by any regulator; Sanofi originally gained it through its ~$1.1B acquisition of Kymab in 2021.

Rocatinlimab (AMG 451 / KHK4083) is an investigational anti-OX40 monoclonal antibody developed by Kyowa Kirin and Amgen for moderate-to-severe atopic dermatitis (eczema). Unlike amlitelimab, which blocks the OX40 ligand (OX40L) on antigen-presenting cells without depleting cells, rocatinlimab binds the OX40 receptor directly on activated pathogenic T cells and reduces (depletes) them - a 'T-cell rebalancing' approach meant to reset the immune drivers of chronic inflammation rather than continuously neutralize a single cytokine. In the large Phase 3 ROCKET program the drug met its co-primary endpoints: in ROCKET-IGNITE (NCT05398445; 769 adults, added to topical therapy) week-24 EASI-75 reached about 42% (higher dose) and 36% (lower dose) versus roughly 13% on placebo, and vIGA-AD 0/1 reached about 24% and 19%; in the ROCKET-HORIZON monotherapy study (NCT05651711) EASI-75 was about 33% versus 14% on placebo, though the drug showed no superiority over dupilumab. The pooled Phase 3 results were published in The Lancet in 2025. Despite hitting its endpoints, the program then unraveled on two fronts: in January 2026 Amgen ended the collaboration on strategic-portfolio grounds and returned global rights to Kyowa Kirin, and on March 3, 2026 Kyowa Kirin discontinued ALL rocatinlimab clinical trials - across atopic dermatitis, prurigo nodularis and uncontrolled asthma - after a safety review identified cases of Kaposi's sarcoma (one newly confirmed and one suspected, in addition to a previously confirmed case) that suggested a possible mechanistic link to OX40-pathway modulation. Rocatinlimab is investigational, was never approved by any regulator, and its clinical development has been halted.

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.