Results from Phase 3 donidalorsen trial expected in first half of 2024
Enrollment complete in OASIS-HAE study
Ionis Pharmaceuticals has finished enrollment in a Phase 3 clinical trial testing the ability of its experimental therapy donidalorsen to prevent swelling attacks in people with hereditary angioedema (HAE) types 1 or 2.
Results from the placebo-controlled study, dubbed OASIS-HAE (NCT05139810), are expected in the first half of 2024. If positive, they will be used to support regulatory applications for the therapy’s approval for HAE.
“By completing enrollment in the Phase 3 study, we are one step closer to bringing a potentially transformative and differentiated prophylactic [preventive] treatment to HAE patients,” Richard Geary, PhD, executive vice president and chief development officer at Ionis, said in a company press release. “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.”
In HAE, swelling attacks are triggered by excess levels of the signaling molecule bradykinin, which is produced by a protein called kallikrein. Donidalorsen is designed to interfere with kallikrein production, thereby lowering bradykinin levels and preventing swelling attacks.
Ionis conducted a Phase 2 trial (NCT04030598) that compared 80 mg of donidalorsen against a placebo injected under the skin monthly for 17 weeks (nearly four months) in 20 adults with HAE type 1 or 2.
Compared with a placebo, donidalorsen reduced the rate of swelling attacks by 90% after the first dose and by 97% after the second, results showed. Patients also reported significant improvements in their quality of life.
Results of donidalorsen treatment
After completing the trial, all participants opted to enroll in an open-label extension study (NCT04307381), where they’re being treated with donidalorsen for up to about four years. For most of it, the patients will receive flexible doses of the therapy, once a month or once every two months.
One-year data from the extension showed swelling rates remain consistently low.
Top-line two-year data from the extension are expected to be presented at a future medical gathering. Donidalorsen continued to show favorable safety and efficacy profiles after two years, with “an overall sustained mean reduction in HAE attack rates of 96% … across dosing groups” the company said.
“We are … encouraged by the long-term safety and durable efficacy results seen in patients treated for two years in our ongoing open-label extension study,” Geary said.
The Phase 3 OASIS-HAE trial, launched in 2021, enrolled 84 people with HAE, ages 12 and older. Participants are being randomly assigned to one of two groups. In one, patients will be given either donidalorsen or a placebo every four weeks. In the other group, donidalorsen or a placebo will be given every eight weeks.
The main goal is to assess the impact of treatment on swelling attacks after about six months. After OASIS-HAE, participants may receive donidalorsen for up to three additional years in a global, open-label study (NCT05392114).
Patients who haven’t participated in OASIS-HAE and have been on stable preventive treatment with Takhzyro (lanadelumab), Orladeyo (berotralstat), or under-the-skin injections of an C1-esterase inhibitor for at least three months may enter the long-term trial. Recruitment is ongoing at more than 30 sites across North America, Europe, Turkey, and Israel.