Japan Grants Orphan Drug Status to Rilzabrutinib for IgG4 Disease

The Ministry of Health, Labour and Welfare has granted orphan drug designation to rilzabrutinib, an investigational oral therapy, for the treatment of IgG4-related disease (IgG4-RD). The designation highlights Japan’s recognition of the urgent need for new treatment options for the rare, chronic condition, which can cause progressive damage to multiple organs.

IgG4-related disease is an immune-mediated disorder in which the immune system mistakenly attacks various tissues and organs, potentially affecting the pancreas, bile ducts, salivary glands, kidneys, and other organs. The disease can lead to inflammation, fibrosis, and significant organ dysfunction if not effectively managed. Treatment options remain limited in Japan, and many patients rely on long-term glucocorticoid therapy, which can be associated with significant side effects.

The orphan drug designation is granted by the Japanese government to encourage the development of therapies targeting rare diseases with unmet medical needs. Medicines that receive this status may benefit from regulatory support measures such as prioritized consultations, financial incentives, and potential accelerated review pathways during development.

Rilzabrutinib is a novel, oral, reversible covalent inhibitor of Bruton’s tyrosine kinase (BTK), an enzyme that plays a key role in immune cell signaling. By targeting BTK, the therapy is designed to modulate abnormal immune responses believed to contribute to diseases like IgG4-RD.

Clinical data supporting rilzabrutinib’s potential in IgG4-related disease were generated in a Phase 2 clinical study (NCT04520451). Results from the trial were presented at the European Alliance of Associations for Rheumatology Congress in 2025. According to the study findings, patients treated with rilzabrutinib for 52 weeks experienced reductions in disease flares and improvements in several disease markers. The treatment also helped reduce reliance on glucocorticoids, which are commonly used to control inflammation in IgG4-RD.

The therapy demonstrated a safety profile consistent with previous studies conducted in other indications, with no new safety concerns identified. The most frequently reported treatment-emergent adverse events occurring in more than 10 percent of participants included diarrhea, COVID-19 infection, dizziness, dry mouth, and nausea.

Further clinical evaluation is ongoing. Rilzabrutinib is currently being assessed in a Phase 3 trial known as the RILIEF study (NCT07190196), which aims to confirm the therapy’s safety and efficacy in patients with IgG4-related disease.

Beyond IgG4-RD, rilzabrutinib is being studied in several other rare immune-mediated conditions. In 2025, the drug received regulatory approval for the treatment of Immune Thrombocytopenia (ITP) in the United States, European Union, and the United Arab Emirates. The therapy is also currently under regulatory review for ITP in Japan.

Additionally, rilzabrutinib has received several expedited regulatory designations worldwide for multiple indications, including Warm Autoimmune Hemolytic Anemia and Sickle Cell Disease. However, aside from its approved use in ITP in certain regions, these other potential applications remain investigational and are still undergoing clinical and regulatory evaluation.