Ionis initiates Phase 3 clinical program of donidalorsen in patients with hereditary angioedema

CARLSBAD, Calif. – Ionis Pharmaceuticals, Inc. (NASDAQ: IONS), the leader in RNA-targeted therapies, announced today initiation of OASIS-HAE, the registrational study in the donidalorsen (formerly IONIS-PKK-LRx) Phase 3 clinical program. Donidalorsen is an investigational antisense medicine designed to reduce the production of prekallikrein, which plays a key role in the activation of inflammatory mediators associated with acute attacks of hereditary angioedema (HAE). Donidalorsen uses Ionis’ LIgand-Conjugated Antisense, or LICA, technology.

“Initiating the Phase 3 program for donidalorsen moves us one step closer to bringing a potential best-in-class prophylactic treatment to market for people with HAE globally experiencing recurrent painful and severe HAE attacks,” said Kenneth Newman, M.D., M.B.A., Ionis’ vice president of clinical development and leader of the immunology and pulmonology franchise. “Advancing this program underscores our commitment to the HAE patient community to deliver transformative treatments.”

OASIS-HAE is a double-blind, randomized, placebo-controlled registrational study in up to 84 patients with hereditary angioedema, Types 1 and 2. Patients will be randomized to receive monthly or bi-monthly subcutaneous donidalorsen for 25 weeks. Following the placebo-controlled portion of the study, patients may enter the 52-week open-label extension study.

New Phase 2 data recently presented at ACAAI highlighted an overall reduction in moderate to severe attacks, and a reduction in these attacks starting with the second dose. For the final month of the study, all donidalorsen treated patients were attack-free. In this study, donidalorsen was safe and well tolerated.

For more information on the OASIS-HAE clinical study please visit

About Donidalorsen Phase 2 study

In the Phase 2 clinical study, 20 adults with Type 1 or Type 2 HAE were randomized and received either donidalorsen 80mg (n=14) or placebo (n=6) subcutaneously once monthly for 17 weeks. The primary endpoint was the reduction of monthly HAE attacks compared to placebo. Secondary endpoints included the reduction of monthly attacks in weeks five to 17, reduction in the number of moderate or severe attacks in weeks one to 17, the number of moderate or severe attacks in weeks five to 17 and the number of attacks requiring acute therapy in weeks five to 17. The majority of adverse events during the study were mild with a frequency that was similar between groups. The most common treatment-emergent adverse events (TEAEs) were headache and nausea, which were seen more frequently in the placebo arm compared to the active treatment arm.

About Hereditary Angioedema

HAE is a rare and potentially fatal genetic disease that is characterized by rapid and painful attacks of inflammation in the hands, feet, limbs, face, abdomen, larynx and trachea. HAE affects approximately 20,000 patients in the U.S. and Europe and can be fatal if swelling occurs in the larynx. In patients with frequent or severe attacks, doctors may use prophylactic treatment approaches to prevent and reduce the severity of HAE attacks.

About Ionis Pharmaceuticals, Inc.

For more than 30 years, Ionis has been the leader in RNA-targeted therapy, pioneering new markets and changing standards of care with its novel antisense technology. Ionis currently has three marketed medicines and a premier late-stage pipeline highlighted by industry-leading neurological and cardiometabolic franchises. Our scientific innovation began and continues with the knowledge that sick people depend on us, which fuels our vision of becoming one of the most successful biotechnology companies.

To learn more about Ionis, visit and follow us on twitter @ionispharma.


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