Japan’s Ministry of Health, Labour And Welfare Grants Orphan Drug Status To Rilzabrutinib After Positive Phase 2 Results In IgG4-Related Disease

The Ministry of Health, Labour and Welfare (MHLW) in Japan has granted orphan drug designation to rilzabrutinib, an oral and reversible covalent Bruton’s tyrosine kinase (BTK) inhibitor, for the treatment of IgG4-related disease (IgG4-RD). This designation is given to medicines developed for rare diseases with limited available treatment options. IgG4-RD is a chronic, progressive, immune-mediated condition in which the immune system attacks various organs and tissues, leading to inflammation, damage, and potential long-term complications. In Japan, patients with IgG4-RD still face significant unmet medical needs due to the lack of effective therapies.

Rilzabrutinib has been studied for IgG4-RD in a Phase 2 clinical trial (NCT04520451), with results shared at the 2025 European Alliance of Associations for Rheumatology congress. In this study, patients received rilzabrutinib for 52 weeks, and the treatment showed promising benefits. It helped reduce disease flares, improved several disease-related markers, and lowered the reliance on glucocorticoids, which are commonly used but associated with long-term side effects. 

The safety profile in IgG4-RD was similar to what has been seen in earlier studies of rilzabrutinib in other conditions. No new safety concerns emerged during the trial. The most common treatment-emergent adverse events reported in more than 10% of patients included diarrhea, COVID-19, dizziness, dry mouth, and nausea. Rilzabrutinib is now being further evaluated in the RILIEF Phase 3 study (NCT07190196) for IgG4-RD.

Beyond IgG4-RD, rilzabrutinib is being researched across several rare immune-mediated diseases. In 2025, it received regulatory approval for immune thrombocytopenia (ITP) in the United States, the European Union, and the United Arab Emirates. The medicine is also under review in Japan for its use in ITP. Globally, rilzabrutinib has earned multiple expedited regulatory designations for different conditions, including ITP, IgG4-RD, warm autoimmune hemolytic anemia (wAIHA), and sickle cell disease (SCD). Except for the approvals already granted for ITP in the U.S., EU, and UAE, all other uses of rilzabrutinib remain investigational and are not yet approved by any regulatory authority.

Rilzabrutinib, marketed as Wayrilz in regions where it is approved, is designed using TAILORED COVALENCY technology. It works by selectively inhibiting BTK, which is found in B cells, macrophages, and other immune cells. Because BTK plays a central role in several immune-mediated and inflammatory processes, blocking this pathway may help restore immune balance and reduce harmful immune activity. This mechanism positions rilzabrutinib as a potential option for treating a range of rare immune-mediated or inflammatory diseases. The medicine is already approved for immune thrombocytopenia in the U.S., EU, and UAE, and review for its approval in Japan is ongoing.

IgG4-related disease itself is a chronic and relapsing condition that can affect almost any organ in the body. Patients often experience repeated flare-ups marked by periods of worsening symptoms. Because the condition is rare and frequently difficult to diagnose, particularly in its early stages, its true global prevalence is still not known. Without timely treatment, IgG4-RD can lead to irreversible tissue damage and organ dysfunction, making the need for effective, targeted therapies especially important.