Ionis Reports Positive Topline Results from Phase 3 HAE Study

Rare Daily Staff

Ionis Pharmaceuticals reported positive topline results for its Phase 3 OASIS-HAE study of its experimental therapy donidalorsen in people with the rare and life-threatening condition hereditary angioedema.

The trial met its primary endpoint of reduction in rate of angioedema attacks in patients treated with donidalorsen via subcutaneous injection dosed every four weeks or every 8 weeks, compared to placebo.

In addition, the trial showed donidalorsen achieved statistical significance on all secondary endpoints in the every four-week group and key secondary endpoints in the every eight group.

Donidalorsen demonstrated a favorable safety and tolerability profile in the study, and there were no serious adverse events in the patients treated with donidalorsen, the company said.

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. Donidalorsen is an investigational RNA-targeted prophylactic medicine designed to precisely target and silence the production of prekallikrein, interrupting the pathway that leads to HAE attacks.

Donidalorsen is an RNA investigational lIgand-conjugated antisense (LICA) medicine designed to precisely target and silence the production of prekallikrein, interrupting the pathway that leads to HAE attacks. prekallikrein plays an important role in activating inflammatory mediators associated with acute attacks of HAE. By silencing the production of prekallikrein, donidalorsen could be an effective prophylactic approach to treating HAE.

Based on these data, Ionis said it is preparing to apply to the U.S. Food and Drug Administration to market donidalorsen. Otsuka, which has exclusive rights to commercialize donidalorsen in Europe, is preparing to submit a marketing authorization application to the European Medicines Agency. Donidalorsen received Orphan Drug Designation in the U.S., and the Orphan Drug Designation procedure in the European Union is ongoing.

Ionis plans to present the Phase 3 OASIS-HAE results at an upcoming medical congress by mid-year. Ionis also plans to share results from the Phase 3 OASIS-Plus study by mid-year, which 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.

“Based on these results and the durable efficacy and favorable safety data seen in the ongoing phase 2 open-label extension study, we believe donidalorsen, if approved, could be an attractive new treatment option for patients with HAE, many of whom continue to experience unpredictable, painful and severe breakthrough attacks despite currently available prophylactic treatments,” said Kenneth Newman, senior vice president, head of clinical development at Ionis.

Photo: Kenneth Newman, senior vice president, head of clinical development at Ionis.