Sanofi’s rilzabrutinib takes Orphan Drug Designation in Japan for IgG4-related disease

Sanofi (EURONEXT: SAN; NASDAQ: SNY), the Paris-headquartered biopharma company, announced that Japan’s Ministry of Health, Labour and Welfare (MHLW) has granted orphan drug designation to rilzabrutinib for the treatment of IgG4-related disease (IgG4-RD). Rilzabrutinib is an oral, reversible covalent Bruton’s tyrosine kinase (BTK) inhibitor acquired by Sanofi via the purchase of Principia Biopharma. The rilzabrutinib orphan drug designation in Japan marks the third such designation globally for the molecule in this indication, following prior designations in other jurisdictions.

Japan’s orphan drug designation system, administered by the MHLW, provides a set of incentives intended to facilitate development of therapies for rare diseases. These include priority review during the regulatory assessment process, extended re-examination periods that function analogously to market exclusivity, financial subsidies covering a portion of clinical development costs, and tax credits on research expenditures.

IgG4-related disease is a chronic, relapsing, immune-mediated condition in which fibroinflammatory infiltration can affect virtually any organ system, leading to progressive tissue damage and, in some cases, organ failure. The global prevalence of IgG4-RD remains poorly characterized owing to diagnostic heterogeneity and frequent misclassification. A claims-based analysis of commercially insured adults in the United States provided incidence and prevalence estimates, but these likely undercount true disease burden given the challenges of case ascertainment.

The current standard of care relies on glucocorticoids as first-line therapy, supplemented in refractory or relapsing cases by B-cell depletion with rituximab. As a review of IgG4-RD treatment has noted, the field lacks approved therapies that durably prevent flares while minimizing glucocorticoid dependence. Amgen’s inebilizumab, an anti-CD19 monoclonal antibody, has been evaluated in the MITIGATE trial for IgG4-RD and represents another candidate under active investigation.

The MHLW designation for Sanofi rilzabrutinib was supported by data from a Phase II study (NCT04520451), which enrolled 27 patients and completed in October 2024. Results presented at the European Alliance of Associations for Rheumatology 2025 congress showed that treatment with rilzabrutinib over 52 weeks reduced disease flares and disease activity markers while decreasing the need for glucocorticoid rescue. Treatment-emergent adverse events reported in more than 10% of patients included diarrhea, COVID-19, dizziness, dry mouth, and nausea, with no new safety signals relative to the molecule’s profile in other indications.

Rilzabrutinib IgG4-RD development has now advanced to the RILIEF Phase III study (NCT07190196), which began recruiting in September 2025 with a target enrollment of 124 patients. The primary endpoint is time to first adjudicated clinical disease flare, with estimated study completion in December 2030.