Otsuka Pharmaceutical Co., Ltd. (Otsuka) announces that the European Medicines Agency (EMA) has accepted for review the Marketing Authorisation Application (MAA) for the hereditary angioedema（HAE）drug candidate donidalorsen (generic name; development code is ISIS 721744) for routine prevention of recurrent attacks of HAE in adults and adolescents aged 12 years and older. The drug was discovered and developed by Ionis Pharmaceuticals, Inc. (Ionis), a leader in RNA-targeted medicines based in California, as a treatment for hereditary angioedema attacks.

HAE is an autosomal-dominant genetic disease characterized by unpredictable and frequently severe swelling of the skin, gastrointestinal (GI) tract, upper respiratory tract, face, and throat. Edema of the GI tract and larynx can cause abdominal pain and breathlessness, and in severe cases, may be life-threatening. This disease is rare, occurring in approximately 1 in 50,000 people, and is thought to have no racial predilection; approximately 75 percent of cases are familial. （Guideline for HAE 2023 by the Japanese Association for Complement Research）

Donidalorsen is an investigational RNA-targeted medicine designed to reduce the production of prekallikrein, or PKK, interrupting the pathway that leads to HAE attacks. The Phase 2 study demonstrated efficacy in reducing HAE attacks and a favorable safety and tolerability profile. In the Phase 3 OASIS-HAE and OASISplus studies, donidalorsen delivered positive data across multiple measures of disease including significant and sustained reduction in mean monthly HAE attack rate, including when self-administered via autoinjector. Orphan drug designation has been received in the U.S. and EU, and in November 2024, Ionis announced that the U.S. Food and Drug Administration (FDA) had accepted for review a New Drug Application (NDA) for donidalorsen.

Otsuka entered into a licensing agreement with Ionis in December 2023 in which Otsuka acquired exclusive rights to commercialize donidalorsen in Europe. Subsequently, in June 2024, Otsuka acquired exclusive commercial rights covering the Asia-Pacific region, including Japan. Otsuka is globally deploying rare disease treatments targeting conditions such as autosomal dominant polycystic kidney disease (ADPKD). By delivering this medication to patients with HAE in Europe and in Asia-Pacific, we are committed to addressing unmet medical needs.