Otsuka Pharmaceutical Co., Ltd.

December 19, 2023

Otsuka and Ionis Enter into Licensing Agreement Covering Europe for
Donidalorsen in Hereditary Angioedema

Otsuka Pharmaceutical Co., Ltd. (Otsuka) and Ionis Pharmaceuticals, Inc. (Ionis), a leader in RNA-targeted therapy based in California, announce that the two companies have entered into a license agreement for Otsuka to acquire exclusive marketing rights to Ionis hereditary angioedema(HAE) drug candidate donidalorsen (generic name) in Europe.

HAE is a rare and life-threatening, autosomal-dominant genetic disease characterized by unpredictable and frequently severe swelling of the skin, gastrointestinal (GI) tract, upper respiratory system, face, and throat, which can be life-threatening. Edema of the gastrointestinal tract and larynx can cause abdominal pain and breathlessness, and in severe cases, death may result from suffocation. The disease onset age for most cases occurs during the teenage years, and it is estimated to affect more than 20,000 patients in the U.S. and Europe.(Weller K, et al. Allergy. 2016;71(8): 1203-1209)

Donidalorsen is an investigational ligand-conjugated antisense (LICA) medicine designed to target the prekallikrein, or PKK, pathway. PKK plays an important role in activating inflammatory mediators associated with acute attacks of hereditary angioedema (HAE). The Phase 2 study demonstrated efficacy in reducing HAE attacks and a favorable safety and tolerability profile. Ionis is currently conducting a global phase 3 study, and Orphan Drug Designation has been received in the U.S.

Under the terms of the agreement, Otsuka will pay Ionis an upfront payment of U.S. $65 million, plus milestone payments based on achievement of regulatory and sales targets. Ionis is also eligible to earn royalties on product sales. Otsuka will apply for regulatory approval and exclusively commercialize the product in Europe.

"We are excited to collaborate with Otsuka given their proven results in bringing rare disease medicines to patients in Europe," said Brett P. Monia, Ph.D., Ionis' chief executive officer. "This agreement is aligned with our strategy to initially focus our commercialization efforts on the U.S. market. We are encouraged by the strong product profile of donidalorsen to date and look forward to reporting pivotal topline Phase 3 donidalorsen results in HAE in the first half of next year."

Makoto Inoue, president and representative director of Otsuka Pharmaceutical Co., Ltd. commented, "Otsuka has developed drugs in Europe for rare diseases such as autosomal dominant polycystic kidney disease (ADPKD). Through this collaboration with Ionis, a leader in RNA-targeted therapy, if regulatory approval is received, we look forward to bringing donidarorsen to patients in Europe to address the unmet medical needs of patients with HAE."