Dawnzera (donidalorsen) approved in the U.S. as first and only RNA-targeted prophylactic treatment for hereditary angioedema – Ionis Pharmaceuticals

Ionis Pharmaceuticals,Inc. announced that the FDA has approved Dawnzera (donidalorsen) for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adult and pediatric patients 12 years of age and older. Dawnzera is the first and only RNA-targeted medicine approved for HAE, designed to target plasma prekallikrein (PKK), a key protein that activates inflammatory mediators associated with acute attacks of HAE. Dawnzera 80mg is self-administered via subcutaneous autoinjector once every four (Q4W) or eight weeks (Q8W).

The approval of Dawnzera was based on positive results from the Phase III global, multicenter, randomized, double-blind, placebo-controlled OASIS-HAE study in patients with HAE. The study met its primary endpoint, with Dawnzera Q4W significantly reducing monthly HAE attack rate by 81% compared to placebo over 24 weeks. Mean attack rate reduction increased to 87% when measured from the second dose, a key secondary endpoint. Additionally, Dawnzera Q4W reduced moderate-to-severe HAE attacks by ~90% over 24 weeks when measured from the second dose.

These results are bolstered by the ongoing OASISplus open-label extension (OLE) study, in which Dawnzera Q8W had a similar effect as Q4W over time. Dawnzera demonstrated 94% total mean attack rate reduction from baseline across both dosing groups after one year in the OLE.

The OASISplus study also includes a switch cohort evaluating Dawnzera Q4W in patients previously treated with lanadelumab, C1-esterase inhibitor or berotralstat for at least 12 weeks. Switching to Dawnzera reduced mean HAE attack rate by 62% from prior prophylactic treatment over 16 weeks, with no mean increase in breakthrough attacks observed during the switch. A total of 84% of patients surveyed preferred Dawnzera over their prior prophylactic treatment, citing better disease control, less time to administer and less injection site pain or reactions.

Across clinical studies, Dawnzera demonstrated a favorable safety and tolerability profile. The most common adverse reactions (incidence ≥ 5%) were injection site reactions, upper respiratory tract infection, urinary tract infection and abdominal discomfort.

Dawnzera will be available in the U.S. in the coming days.

“DAWNZERA represents a significant advance for people living with HAE who need improved treatment options. With strong and durable efficacy, convenient administration and the longest dosing option available, we believe DAWNZERA will be the prophylactic treatment of choice for many people living with HAE. Importantly, the recently published switch data empowers patients and physicians with a roadmap for switching to DAWNZERA from other prophylactic therapies,” said Dr. Brett P. Monia, chief executive officer, Ionis. “At Ionis, we are dedicated to turning groundbreaking science into life-changing medicines. With the early success of our first independent launch of TRYNGOLZA for familial chylomicronemia syndrome (FCS), and now with DAWNZERA, our second independent medicine approved in less than nine months, we are proudly delivering on that vision. To the patients, families, advocacy partners and investigators who helped make this moment a reality, we express our deepest gratitude.”

“As the first FDA-approved RNA-targeted therapy for HAE, DAWNZERA represents a welcome advance in therapeutic options for preventing attacks. This approval gives people living with HAE and their physicians another important choice for aligning treatment with individual needs,” said Anthony J. Castaldo, CEO & chairman of the board, U.S. Hereditary Angioedema Association (HAEA) and Hereditary Angioedema International (HAEi).

“People living with HAE manage this condition for all their lives, and many continue to face unpredictable, painful and dangerous breakthrough attacks even with current treatments. Durable efficacy is essential in maintaining long-term disease control,” said Dr. Marc Riedl, clinical director, U.S. HAEA Angioedema Center; University of California, San Diego; OASIS-HAE and OASISplus trial investigator. “DAWNZERA is positioned to help meet patient needs, providing substantial and sustained reduction of HAE attacks, continued improvement over time and reduced burden of treatment.”