The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to Wayrilz (rilzabrutinib), an investigational oral, reversible Bruton’s Tyrosine Kinase (BTK) inhibitor, for the treatment of warm Autoimmune Haemolytic Anaemia (wAIHA). The Japanese Ministry of Health, Labour and Welfare has also granted orphan drug designation to rilzabrutinib for the same indication.

The regulatory recognitions are supported by clinical findings from the ongoing Phase IIb LUMINA 2 study evaluating the efficacy and safety of rilzabrutinib in patients with wAIHA. In parallel, the Phase III LUMINA 3 trial (NCT07086976) is underway to assess rilzabrutinib versus placebo in individuals with the condition. Currently, there are no approved therapies that directly target the underlying cause of wAIHA, a rare autoimmune disorder that leads to premature destruction of red blood cells and can result in anaemia, severe fatigue and potential organ complications.

The FDA’s breakthrough therapy designation is intended to fast-track the development and review of medicines for serious or life-threatening diseases when preliminary clinical evidence suggests meaningful improvement over existing treatment options. Orphan designation in Japan is granted to therapies addressing rare conditions with significant unmet medical needs.

Karin Knobe, Global Head of Development, Rare Diseases, said, “These recognitions highlight the critical unmet need that persists for people living with wAIHA. Receiving these designations reinforces our commitment to advancing innovative treatments for rare diseases where approved options remain limited or absent.”

Rilzabrutinib is already approved in the US, European Union and the United Arab Emirates under the brand name Wayrilz for the treatment of Immune Thrombocytopenia (ITP) in adults. The therapy is currently under regulatory review for ITP in Japan. Apart from the approved ITP indications, all other uses remain investigational and have not yet been approved by regulatory authorities.

The FDA has previously granted orphan drug designation to rilzabrutinib for autoimmune haemolytic anaemia, IgG4-related disease (IgG4-RD) and sickle cell disease (SCD), as well as fast track designation for ITP and IgG4-RD. The European Union has also awarded orphan status for ITP, autoimmune haemolytic anaemia and IgG4-RD.

Warm autoimmune haemolytic anaemia accounts for more than half of all autoimmune haemolytic anaemia cases and is considered potentially life-threatening. The condition arises from immune system dysfunction, where autoantibodies attack and destroy red blood cells faster than they can be replaced. In the US and EU, autoimmune haemolytic anaemia affects an estimated four to 24 individuals per 100,000, while in Japan prevalence ranges from three to 10 per million. Patients often experience fatigue, dizziness, shortness of breath and palpitations and may face serious complications such as thromboembolism.

Rilzabrutinib is a novel oral BTK inhibitor developed using tailored covalency technology, designed to selectively inhibit BTK while modulating multiple immune pathways. By targeting B cells, macrophages and other innate immune cells, the therapy aims to restore immune balance in rare immune-mediated diseases.