Ionis Pharmaceuticals publishes results of OASISplus study

Ionis Pharmaceuticals (IONS) announced that results from the Phase 3 OASISplus prospective switch study of donidalorsen in patients with hereditary angioedema were published in The Journal of Allergy and Clinical Immunology In Practice. Results indicate that patients who switched to donidalorsen from prior prophylactic treatments showed a 62% further reduction in mean monthly HAE attack rate from baseline, and 84% of patients surveyed reported preference for donidalorsen. The new drug application for donidalorsen to prevent attacks of HAE in adult and pediatric patients 12 years of age and older is currently under review with the U.S. Food and Drug Administration (FDA), with a target action date of August 21. The Phase 3 OASISplus study included an open-label extension cohort of patients continuing from the OASIS-HAE trial, as well as a prospective cohort to assess patients switching from both oral and injectable long-term prophylactic treatments to donidalorsen. The OASISplus switch cohort evaluated the safety and efficacy of donidalorsen administered every four weeks in patients who were previously treated with lanadelumab, C1-esterase inhibitor or berotralstat for at least 12 weeks prior to entering the study. Patients entered a 10-week baseline period during which they remained on their prior HAE prophylactic therapy before switching to donidalorsen. Patients followed a pre-defined specific protocol to transition from their prior therapy to donidalorsen with no mean increase in breakthrough attacks observed during the switch. After 16 weeks of treatment with donidalorsen, patients experienced a 62% overall further reduction in mean HAE attack rate compared to baseline from their prior prophylactic treatment. HAE attack rate decreased by 65%, 41% and 73% for patients switching from lanadelumab, C1INH and berotralstat, respectively, after switching to donidalorsen. The majority (84%) of patients reported a preference for donidalorsen over their prior therapy, citing better disease control, less time to administer, and less injection site pain or reactions. More patients reported well-controlled disease (93% versus 67% at baseline) after switching to donidalorsen, as measured by the Angioedema Control Test (AECT). The AECT is a standardized patient-reported questionnaire consisting of four questions related to the frequency, unpredictability and control of angioedema, designed to help identify patients with poor disease control. Quality-of-life measures also improved regardless of prior therapy. Donidalorsen was well-tolerated, with no serious treatment emergent adverse events (TEAEs) related to donidalorsen. Most adverse events (AEs) were mild or moderate in severity, and injection site reactions were the most common AE. One patient discontinued due to a TEAE not related to donidalorsen. Ionis previously reported positive results from the Phase 3 OASIS-HAE and OASISplus studies. Data from both studies were first presented at the 2024 European Academy of Allergy and Clinical Immunology (EAACI) Annual Congress in Valencia, Spain, and results from OASIS-HAE were published in The New England Journal of Medicine.