Ionis Pharmaceuticals announced that the U.S. Food and Drug Administration (FDA) has granted approval for DAWNZERA™ (donidalorsen). The treatment is approved for prophylaxis to avoid hereditary angioedema (HAE) attacks in pediatric and adult patients aged 12 years and older. DAWNZERA is the first RNA-targeting therapy approved for use in this condition. The treatment works by targeting plasma prekallikrein (PKK), a protein involved in the activation of inflammatory mediators associated with acute HAE attacks. DAWNZERA 80mg can be self-administered subcutaneously using an autoinjector once every four weeks (Q4W) or every eight weeks (Q8W).
HAE is a rare but potentially fatal genetic condition that involves repeated episodes of severe swelling, or angioedema, that can occur in the hands, feet, stomach, face, throat or genitals. In the U.S., an estimated 7,000 people suffer from this disease.
“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 Brett P. Monia, Ph.D., 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.”
The FDA’s approval was supported by results from the Phase 3 OASIS-HAE study, a global, multicenter, randomized, double-blind, placebo-controlled study. This study achieved its primary endpoint, with DAWNZERA Q4W reducing monthly attack rates by 81% over 24 weeks compared to placebo. Second dose achieved its endpoint with an 87% mean attack rate reduction. Also, moderate-to-severe HAE attacks decreased by almost 90% over 24 weeks after the second dose.
These results were supported by the OASISplus open-label extension trial. In this trial, DAWNZERA Q8W showed similar efficacy as the Q4W over time. After a year, both groups of patients had a 94% reduction in mean baseline attack rates.
The OASISplus trial also included a switch cohort that studied patients who had already been treated with other treatments like lanadelumab, C1-esterase inhibitor or berotralstat for at least 12 weeks. Transitioning to DAWNZERA for Hereditary Angioedema patients led to a 62% reduction in mean HAE attack rates compared with other prophylactic treatments over 16 weeks. No increase in breakthrough attacks was observed during the switch period. 84% of surveyed patients indicated they preferred DAWNZERA for Hereditary Angioedema over earlier options due to improved disease control, faster administration, and less discomfort at the injection site.
Across multiple clinical studies, DAWNZERA demonstrated a favorable safety and tolerability profile. The most common adverse reactions, reported in at least 5% of patients, included mild injection site reactions, upper respiratory tract infections, urinary tract infections and abdominal discomfort.
“As the first FDA-approved RNA-targeted therapy for HAE, DAWNZERA represents a welcome advance in therapeutic options for preventing attacks. Today’s 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 Marc Riedl, M.D., M.S., 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.”
DAWNZERA will be available in the U.S. in the coming days.
