Ionis Pharmaceuticals has recently announced positive results from the phase 2, 2-year open-label extension study assessing donidalorsen, an investigational ligand-conjugated antisense medicine, as a late-stage prophylactic therapy for hereditary angioedema (HAE). 

Furthermore, the company announced they have completed enrollment in the phase 3 OASIS-HAE study—a multicenter, double-blind, randomized, placebo-controlled study that aims to evaluate the safety and efficacy of donidalorsen in preventing HAE attacks (NCT05139810).

“By completing enrollment in the phase 3 study, we are one step closer to bringing a potentially transformative and differentiated prophylactic treatment to HAE patients,” said Richard S Geary, PhD, executive vice president and chief development officer at Ionis.

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“We are also encouraged by the long-term safety and durable efficacy results seen in patients treated for two years in our ongoing open-label extension study. We look forward to the phase 3 data readout in the first half of 2024 and are advancing our go-to-market preparations to commercialize donidalorsen.”

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The results from the phase 2 open-label extension study (NCT04307381), which will be presented at an upcoming medical congress, continue to support the efficacy and safety of donidalorsen.

The overall sustained mean reduction in HAE attack rates was 96% from baseline through 2 years across dosing groups. Through week 17, monthly treatment with 80 mg of donidalorsen allowed for a 90% reduction in HAE attacks compared with placebo after the first dose, and a 97% reduction in HAE attacks starting with the second dose.

Moreover, donidalorsen led to a significant improvement in patients’ quality of life, as assessed by the Angioedema Quality of Life Questionnaire.

Donidalorsen’s safety and tolerability profile remains favorable with the addition of the 2-year open-label extension data.

The phase 3 OASIS-HAE study will evaluate the safety and efficacy of monthly and bimonthly subcutaneous injections of donidalorsen or placebo in 84 participants, aged 12 years and above, with type 1 or type 2 HAE. Participants were randomized to either cohort A (donidalorsen or placebo every 4 weeks) or cohort B (donidalorsen or placebo every 8 weeks). Then, within each cohort, participants were randomized to receive donidalorsen or matching-placebo.

The primary endpoint of OASIS-HAE is the time-normalized number of investigator-confirmed HAE attacks from week 1 to 25.


Ionis announces positive donidalorsen late-stage clinical progress in HAE. News release. Ionis Pharmaceuticals, Inc.; June 1, 2023.