The market for FcRn (neonatal Fc receptor) inhibitors is poised for substantial growth, driven by increasing diagnoses of autoimmune diseases and the advancement of novel therapies. These inhibitors offer a targeted approach to reducing pathogenic immunoglobulin G (IgG) levels, presenting a less invasive alternative to traditional treatments like plasma exchange (PLEX) and intravenous immunoglobulin (IVIg) for various autoimmune conditions.
Clinical Advancements in FcRn Inhibition
Several companies are actively developing FcRn inhibitors, with promising results in clinical trials. Immunovant recently announced positive results from its Phase IIa trial of batoclimab in Graves' Disease and has received FDA clearance for a pivotal trial of IMVT-1402 in Graves' Disease, expected to begin in December 2024. Johnson & Johnson's nipocalimab received fast-track designation from the FDA to reduce fetal and neonatal alloimmune thrombocytopenia (FNAIT) risk and reported positive Phase II/III results in adolescents with generalized myasthenia gravis (gMG), demonstrating significant IgG reduction and improvements in MG-ADL and QMG scores over 24 weeks.
Efgartigimod alfa (VYVGART), developed by Argenx, is a first-in-class antibody fragment targeting FcRn and has shown established dominance in the myasthenia gravis market. In 2023, VYVGART and VYVGART SC generated global net product revenues of USD 908 million and USD 246 million, respectively. UCB Biopharma's RYSTIGGO (rozanolixizumab-noli) received FDA approval in June 2023 for generalized myasthenia gravis in adults who are anti-acetylcholine receptor (AChR) or anti-muscle-specific kinase (MuSK) antibody positive.
FcRn Inhibitors in Development
Batoclimab, a fully human anti-FcRn mAb developed by Immunovant, is being evaluated as a low-volume subcutaneous injection for various IgG-mediated autoimmune disorders, including myasthenia gravis, thyroid eye disease, chronic inflammatory demyelinating polyneuropathy (CIDP), and Graves' disease. Phase II studies have shown that batoclimab can quickly and significantly alleviate patients' symptoms and improve quality of life by accelerating the degradation of autoantibodies.
Nipocalimab, Johnson & Johnson's investigational high-affinity, fully human, aglycosylated, effectorless monoclonal antibody, is designed to selectively block FcRn to reduce levels of circulating IgG antibodies. It is being studied in rare autoantibody diseases, maternal-fetal diseases, and prevalent rheumatologic diseases. Janssen-Cilag International NV, a Johnson & Johnson company, submitted a Marketing Authorisation Application (MAA) to the European Medicines Agency (EMA) seeking approval of nipocalimab for the treatment of people living with gMG in September 2024.
Market Landscape and Epidemiology
The increasing prevalence of autoimmune diseases is driving the demand for FcRn inhibitors. In 2023, chronic inflammatory demyelinating polyneuropathy (CIDP) affected approximately 21,000 patients in the United States. Graves' disease had an estimated prevalence of around 1,241,720 cases across the EU4 and the UK in 2023, while thyroid eye disease impacted approximately 84,000 patients across the seven major markets (7MM) in 2023.
The greater affinity of FcRn has adverse effects on IgG-mediated autoimmune diseases like rheumatoid arthritis, myasthenia gravis, or pemphigus vulgaris. Targeting FcRn and inhibiting FcRn circulation can improve IgG catabolism, resulting in reduced IgG and pathogenic autoantibody levels, which is anticipated to decrease all autoimmune abnormalities induced by IgG.
With several key players, including Argenx, UCB Biopharma, Pfizer, and others, involved in developing drugs for FcRn inhibitors for various indications such as myositis, myasthenia gravis, fibromyalgia, systemic lupus erythematosus, and others, the maturation of current studies over the next few years will lead to a better understanding of FcRn inhibitors and define their role in the therapy of autoimmune and neurological disorders.
