Sanofi's Rilzabrutinib Gains Regulatory Designations in Japan and U.S. for Rare Diseases
Sanofi's oral BTK inhibitor rilzabrutinib received orphan drug designation in Japan for IgG4-related disease and warm autoimmune hemolytic anemia, while also securing U.S. FDA breakthrough therapy designation for the rare anemia indication.
The Ministry of Health, Labour and Welfare (MHLW) in Japan has granted orphan drug designation to rilzabrutinib, a novel, oral, reversible covalent Bruton's tyrosine kinase (BTK) inhibitor, for IgG4-related disease (IgG4-RD). On February 9, 2026, rilzabrutinib also received U.S. FDA breakthrough therapy designation and orphan drug status in Japan for treating warm autoimmune hemolytic anemia, a rare and potentially life-threatening autoimmune blood disorder.
The designation for IgG4-RD was based on positive data from a phase 2 study of rilzabrutinib in IgG4-RD. This marks the third global orphan drug designation for rilzabrutinib in IgG4-RD. There is still unmet medical need and limited treatment options in Japan for IgG4-RD, a rare, progressive, immune-mediated chronic condition in which the immune system attacks various tissues and organs leading to serious damage.
Rilzabrutinib for the treatment of IgG4-RD was evaluated in a phase 2 study (clinical study identifier: NCT04520451) and results were presented at the European Alliance of Associations for Rheumatology 2025 congress. In IgG4-RD patients, treatment with rilzabrutinib for 52 weeks led to reduction in disease flares and other disease markers and minimized the need for treatment with glucocorticoids. The safety profile of rilzabrutinib in the study was consistent with previous studies in other indications, with no new safety signals observed. Treatment-emergent adverse events reported by more than 10% of patients include diarrhea, COVID-19, dizziness, dry mouth and nausea.
The dual designations for warm autoimmune hemolytic anemia were supported by data from the ongoing LUMINA 2 phase 2b and LUMINA 3 phase 3 trials. The designations highlight the absence of targeted therapies for this condition.
Currently, rilzabrutinib in IgG4-RD is being evaluated in the RILIEF phase 3 study (clinical study identifier: NCT07190196). Rilzabrutinib is being studied across multiple rare immune-mediated diseases. In 2025, it received approval for immune thrombocytopenia (ITP) in the US, the EU, and the UAE, where it is marketed as Wayrilz. Additionally, rilzabrutinib is currently under regulatory review for ITP in Japan.
Rilzabrutinib has received several expedited designations from global regulatory authorities for ITP, IgG4-RD, warm autoimmune hemolytic anemia (wAIHA), and sickle cell disease (SCD). Other than the approved ITP indications in the US, EU, and UAE, these uses of rilzabrutinib are investigational and have not been evaluated by any regulatory authority.
Rilzabrutinib is a novel, oral, reversible covalent BTK inhibitor that has the potential to be an effective new medicine for several rare immune-mediated or inflammatory diseases by working to restore immune balance via multi-immune modulation. BTK, expressed in B cells, macrophages, and other innate immune cells, plays a critical role in multiple immune-mediated disease processes and inflammatory pathways. With the application of the TAILORED COVALENCY technology, rilzabrutinib can selectively inhibit the BTK target.
IgG4-RD is a progressive, relapsing, chronic immune-mediated rare disease, which can manifest in almost every organ and can lead to organ damage and irreversible dysfunction with a sometimes fatal outcome. People with IgG4-RD experience flare-ups of the condition characterized by periods of exacerbated symptoms. Due to its rarity and challenges with diagnosis, the global prevalence of IgG4-RD is unknown.