Japan’s MHLW grants orphan status to rilzabrutinib for IgG4-RD. Phase 2 data show reduced flares; phase 3 ongoing. BTK inhibitor expands from ITP approvals.
Written By: Nikita Jha, Pharm
Reviewed By: Pharmacally Editorial Team
Japan’s Ministry of Health, Labour and Welfare (MHLW) has awarded orphan drug designation to rilzabrutinib, a novel oral reversible covalent Bruton’s tyrosine kinase (BTK) inhibitor, for IgG4-related disease (IgG4-RD). This rare, progressive immune-mediated condition drives the immune system to attack various tissues and organs, causing serious damage with limited treatment options available in Japan.
The designation underscores rilzabrutinib’s promise in addressing unmet needs for IgG4-RD, a relapsing chronic disease that can affect nearly every organ, leading to irreversible dysfunction and potentially fatal outcomes.
Patients often face flare-ups of exacerbated symptoms, yet global prevalence remains unknown due to diagnostic challenges.
Promising data from a phase 2 study (NCT04520451) supported this milestone. Presented at the European Alliance of Associations for Rheumatology 2025 congress, the trial showed rilzabrutinib reduced disease flares, improved markers, and minimized glucocorticoid use over 52 weeks in IgG4-RD patients.
Its safety profile aligned with prior studies no new signals emerged with common treatment-emergent adverse events (>10% of patients) including diarrhea, COVID-19, dizziness, dry mouth, and nausea.
Rilzabrutinib now advances to the phase 3 RILIEF study (NCT07190196) for IgG4-RD. Leveraging TAILORED COVALENCY® technology, the drug selectively inhibits BTK key in B cells, macrophages, and innate immune pathways to restore immune balance across rare immune-mediated diseases.
Building momentum, rilzabrutinib (Wayrilz where approved) gained 2025 approvals for immune thrombocytopenia (ITP) in the US, EU, and UAE, with Japanese review ongoing. It holds expedited designations for ITP, IgG4-RD, warm autoimmune hemolytic anemia (wAIHA), and sickle cell disease (SCD). Beyond approved ITP uses, other indications remain investigational.
This orphan status positions rilzabrutinib as a potential game-changer for IgG4-RD patients worldwide.
References
Press Release: Sanofi’s rilzabrutinib earns orphan drug designation in Japan for IgG4-related disease, 02 March 2026, Press Release: Sanofi’s rilzabrutinib earns orphan drug designation in Japan for IgG4-related disease
Open Label Two-Arm Study to Evaluate Rilzabrutinib in IgG4-Related Disease Participants, ClinicalTrials.gov ID NCT04520451, https://clinicaltrials.gov/study/NCT04520451
About Writer
Nikita Jha BPharm
She is a pharmacy graduate with expertise in clinical research, pharmacovigilance, and medical writing. In her words, she is passionate about translating complex scientific data into clear, accurate healthcare communications that advance drug safety and patient care.