Ionis reports positive OASIS-HAE and OASISplus results for donidalorsen in hereditary angioedema patients

Ionis Pharmaceuticals, Inc. recently announced the successful results from their Phase 3 OASIS-HAE and OASISplus studies of donidalorsen, a drug for treating hereditary angioedema (HAE). These studies showed a significant and continuous reduction in the frequency of HAE attacks and improvements in patients' quality of life with both monthly and bi-monthly dosing regimens. The findings will be shared at the 2024 European Academy of Allergy and Clinical Immunology (EAACI) Annual Congress.

Hereditary angioedema is a rare and potentially lethal genetic disorder marked by recurrent episodes of severe swelling in various parts of the body. Donidalorsen is an investigational RNA-targeted medication intended to decrease the production of prekallikrein (PKK), thereby inhibiting the pathway leading to HAE attacks.

The OASIS-HAE study was a global, multicenter, randomized, double-blind, placebo-controlled trial involving 91 participants aged 12 and above with HAE. Participants were given donidalorsen (80 mg) via subcutaneous injection either every four weeks (Q4W) or every eight weeks (Q8W), or a placebo, for 24 weeks. The study achieved its primary endpoint, showing an 81% reduction in monthly HAE attack rates for those on the Q4W regimen compared to placebo. Additionally, a reduction of 55% was observed for the Q8W regimen.

Secondary endpoints also favored donidalorsen, with an 87% reduction in mean monthly HAE attack rates for the Q4W group compared to placebo. Severe to moderate attacks were reduced by 89%, and attacks necessitating acute therapy saw a 92% reduction. Quality of life improvements were measured using the Angioedema Quality of Life Questionnaire (AE-QoL), and the Q8W regimen delivered similar benefits over time regarding attack rate reduction and quality of life measures.

The safety profile of donidalorsen was positive, with no significant treatment-related adverse events reported. The most common adverse events were mild to moderate injection site reactions, with only one patient discontinuing due to noncompliance and a treatment-emergent adverse event (TEAE).

In the OASISplus study, which included an open-label extension (OLE) cohort and a switch cohort, 94% of eligible patients from the OASIS-HAE study continued their treatment. The switch cohort assessed patients transitioning from other prophylactic treatments to donidalorsen. Results indicated a further 62% reduction in mean monthly HAE attacks for patients switching to donidalorsen, with 84% preferring it over their previous treatments. Quality of life measures also continued to improve, with 93% of patients reporting well-controlled disease compared to 67% with prior prophylactic treatments.

No serious safety concerns were noted in the OASISplus study. One patient discontinued due to a TEAE not related to donidalorsen.

Dr. Brett Monia, CEO of Ionis, highlighted the significance of these results, stating that donidalorsen could advance the prophylactic treatment paradigm for HAE patients. Dr. Marc Riedl, a clinical director at the U.S. HAEA Angioedema Center, emphasized the importance of lasting efficacy in treatment options, noting that the study demonstrated patients could switch to donidalorsen without an increased risk of breakthrough HAE attacks.

Ionis plans to file a New Drug Application with the U.S. FDA this year and aims to launch donidalorsen as part of its independent commercial pipeline, pending approval. Otsuka Pharmaceutical Co., Ltd., which holds exclusive commercialization rights in Europe, will also submit a Marketing Authorization Application to the European Medicines Agency.