• Donidalorsen delivered significant and sustained reductions in HAE attacks, with high levels of disease control and improvement in quality of life measures with monthly or every two-month dosing; continued attack rate reduction over time
• In first-of-its-kind prospective analysis, patients switching from prior prophylactic treatment to donidalorsen experienced further reductions in mean monthly HAE attack rates from baseline
• Donidalorsen demonstrated a favorable safety and tolerability profile across all cohorts
• Data to be presented today at EAACI Congress 2024
• Ionis to host webcast on Friday, May 31 at 8:00am ET

CARLSBAD, Calif., May 31, 2024 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) today announced positive results from the Phase 3 OASIS-HAE and OASISplus studies of donidalorsen in patients with hereditary angioedema (HAE) demonstrating significant and sustained reduction in mean monthly HAE attack rates and continued attack rate improvement of >90% with one year of treatment for both monthly or every two-month dosing. Patients who switched to donidalorsen from prior prophylactic treatment also showed 62% further reduction in mean monthly HAE attack rates from baseline, and 84% of patients who switched reported a preference for donidalorsen. Donidalorsen had a favorable safety and tolerability profile across both studies, including when self-administered via an auto-injector. Results will be presented in three late-breaking oral presentations at the 2024 European Academy of Allergy and Clinical Immunology (EAACI) Annual Congress in Valencia, Spain. Based on these data, Ionis is pursuing regulatory approval of donidalorsen as a potential treatment for HAE.

HAE is a rare and potentially life-threatening genetic condition that involves recurrent attacks of severe swelling (angioedema) in various parts of the body, including the hands, feet, genitals, stomach, face and/or throat. Donidalorsen is an investigational RNA-targeted prophylactic medicine designed to reduce the production of prekallikrein (PKK), interrupting the pathway that leads to HAE attacks.

"We're delighted by the results from the OASIS clinical program, which we believe position donidalorsen to advance the prophylactic treatment paradigm for people living with HAE. Despite currently available therapies, people living with HAE still face significant disease burden and new prophylactic treatments are needed," said Brett Monia, Ph.D., chief executive officer of Ionis. "These data underscore the potential of donidalorsen to continually improve HAE attack rates and quality of life over time, positioning donidalorsen as an attractive potential treatment option. In our prospective switch cohort, patients switched to donidalorsen from another prophylactic without increased breakthrough attacks and achieved greater disease control. In fact, a majority of patients who switched reported a preference for donidalorsen. We thank the patients, families and clinicians who participated in these important studies. Based on these results, Ionis will pursue regulatory approval for donidalorsen, and we look forward to launching it as part of our growing independent commercial pipeline, if approved."

OASIS-HAE Study ResultsIn the Phase 3 OASIS-HAE study, patients with HAE were treated with donidalorsen (80 mg) via subcutaneous injection every four weeks (Q4W) (n=45) or every eight weeks (Q8W) (n=23), or placebo (n=22), over 24 weeks.

• The study met its primary endpoint, demonstrating 81% lower monthly HAE attack rate with donidalorsen Q4W compared to placebo over weeks one to 25 (p