Otsuka announces topline results from Ionis’ Phase 3 OASIS-HAE study of investigational donidalorsen in patients with hereditary angioedema
London, UK, 24 January 2024 — Otsuka Pharmaceutical Europe Ltd. (Otsuka) is pleased to announce topline results for the Ionis Phase 3 OASIS-HAE study of donidalorsen in people with hereditary angioedema (HAE). The trial met its primary endpoint of reduction in rate of angioedema attacks in patients treated with donidalorsen (80 mg) via subcutaneous injection dosed every 4 weeks (Q4W) (p<0.001) or every 8 weeks (Q8W) (p=0.004), compared with placebo. In addition, the trial showed donidalorsen achieved statistical significance on secondary endpoints in the Q4W group and Q8W group. Donidalorsen demonstrated a favourable safety and tolerability profile in the study, and there were no serious adverse events in patients treated with donidalorsen.
HAE is a rare and life-threatening genetic disease that causes unpredictable and frequent severe swelling of the skin, gastrointestinal tract, upper respiratory system, face and throat.1–5 Donidalorsen is an investigational RNA-targeted prophylactic medicine designed to precisely target and silence the production of prekallikrein (PKK), interrupting the pathway that leads to HAE attacks.
Otsuka has exclusive rights to commercialise donidalorsen in Europe and is preparing to submit a Marketing Authorisation Application to the European Medicines Agency
(EMA). Ionis is preparing to submit a New Drug Application with the US Food and Drug Administration (FDA). Donidalorsen received Orphan Drug Designation in the USA, and the Orphan Drug Designation procedure in the EU is ongoing.
“The topline results from the Phase 3 OASIS-HAE study are encouraging,” said Andy Hodge, CEO, Otsuka Pharmaceutical Europe. “Despite the availability of other prophylactic treatments, a considerable number of patients with HAE continue to experience unpredictable, painful and severe breakthrough attacks. We believe donidalorsen, if approved, could address this unmet medical need and provide a potential new treatment option for these individuals.”
Otsuka and Ionis are planning to present both the Phase 3 OASIS-HAE results and the OASIS-Plus study mid-year. The OASIS-Plus study includes both the open-label extension of the Phase 3 trial and a separate cohort of patients who have transitioned to donidalorsen from another prophylactic HAE medication (switch cohort).
About the OASIS-HAE study6
The global, multicentre, randomised, double-blind, placebo-controlled, Phase 3 OASIS-HAE study (NCT05139810) enrolled 91 participants, aged 12 and above, with type 1 and type 2 HAE. Participants were randomised in a 2:1 ratio to receive donidalorsen 80 mg or placebo via subcutaneous injection once every four weeks for 24 weeks or donidalorsen 80 mg or placebo via subcutaneous injection once every eight weeks for 24 weeks. Within each cohort, participants were randomised in a 3:1 ratio to receive donidalorsen or matching-placebo. The primary endpoint was the time-normalised number of investigator-confirmed HAE attacks from week one to week 25 compared with placebo. More than 90% of patients completed the OASIS-HAE study. Following completion of the treatment period, over 90% of randomised patients entered the OASIS-Plus open-label extension study.
About the OASIS-Plus study7
The OASIS-Plus open-label extension (OLE) study is a 53-week, global, multicentre study of subcutaneous injections of donidalorsen administered every four weeks (80 mg) or every eight weeks (80 mg) in patients completing the OASIS-HAE trial. These are patients aged 12 and above, with type 1 and type 2 HAE. The study is designed to evaluate the safety and efficacy of extended dosing of donidalorsen following completion of the Phase 3 OASIS-HAE study. The OASIS-Plus switch cohort is evaluating the safety and efficacy of long-term dosing of donidalorsen every four weeks in patients who were previously treated with another prophylactic HAE medication. Additional information about OASIS-Plus (NCT04307381) may be found at ClinicalTrials.gov.
About hereditary angioedema (HAE)
HAE is a rare, autosomal-dominant genetic disease characterised by unpredictable and frequently severe swelling of the skin, gastrointestinal tract, upper respiratory system, face and throat, which can be life-threatening.1–5 In most cases the disease onset occurs during the teenage years, and the worldwide prevalence of this rare disease is estimated to be 1 in 50,000.5,8
About donidalorsen
Donidalorsen is an RNA investigational ligand-conjugated antisense (LICA) medicine designed to precisely target and silence the PKK, interrupting the pathway that leads to HAE attacks. PKK plays an important role in activating inflammatory mediators associated with acute attacks of HAE. By silencing the production of PKK, donidalorsen could be an effective prophylactic approach to treating HAE.
About Otsuka
Otsuka Pharmaceutical is a global healthcare company with the corporate philosophy “Otsuka-people creating new products for better health worldwide”. Otsuka researches, develops, manufactures and markets innovative products, focusing on pharmaceutical products to meet unmet medical needs and nutraceutical products for the maintenance of everyday health. In pharmaceuticals, Otsuka is a leader in the challenging area of mental health and has research programmes in several under-addressed diseases including tuberculosis, a significant global public health issue.
Otsuka Europe employs around 550 people and focuses on psychiatric and neurologic disorders, infectious disease, nephrology, oncology, rare diseases and digital medicines.
Otsuka Pharmaceutical Europe Ltd. is a part of Otsuka Pharmaceutical Company, Ltd., a subsidiary of Otsuka Holdings Co., Ltd. headquartered in Tokyo, Japan.
The Otsuka group of companies employed 47,000 people worldwide with consolidated sales of approximately €12.4 billion and a spend of €1.67 billion on research and development in 2022. For further information on Otsuka, please visit
www.otsuka-europe.com.
About Ionis Pharmaceuticals, Inc.
For more than 30 years, Ionis has been a leader in RNA-targeted therapy, pioneering new markets and changing standards of care. Ionis currently has five marketed medicines and a promising late-stage pipeline highlighted by cardiovascular and neurological franchises. Our scientific innovation began and continues with the knowledge that sick people depend on us, which fuels our vision to become the leader in genetic medicine, utilising a multi-platform approach to discover, develop and deliver life-transforming therapies.
