Hereditary angioedema (HAE), a rare genetic condition characterized by recurrent and unpredictable swelling attacks, is receiving unprecedented attention in 2025 due to the rapid approval of three new treatments by the U.S. Food and Drug Administration (FDA). In a span of just three months, the FDA authorized garadacimab-gxii (Andembry) in June, sebetralstat (Ekterly) in July, and donidalorsen (Dawnzera) in August. These advancements signal a significant shift in the treatment landscape for this often misdiagnosed condition.
HAE affects approximately 1 in 50,000 people globally, with an estimated 6,000 cases in the United States. The disease can lead to life-threatening swelling in various parts of the body, including the face, throat, and abdomen. Delays in diagnosis are common, with a report indicating that up to 90% of HAE-related fatalities occur in undiagnosed patients due to asphyxiation.
At the 2025 American College of Allergy, Asthma, & Immunology (ACAAI) Annual Scientific Meeting in Orlando, Florida, Dr. Daniel Soteres from the University of Colorado Health Sciences Center emphasized the importance of having multiple treatment options. He noted, “Every patient has an individual set of values, an individual health literacy. Their needs change over time.”
Prior to June 2025, there were nine FDA-approved therapies for HAE, consisting of four preventive and four acute attack treatments. The new approvals bring the total to twelve, enhancing the ability to create personalized treatment plans for patients. The existing therapies primarily work by replacing C1-inhibitor proteins, blocking bradykinin, or inhibiting kallikrein, with administration routes including intravenous, subcutaneous, and oral methods.
Breakthrough Treatments Transform HAE Management
The approval of garadacimab-gxii on June 16, 2025, marked a milestone as the first treatment targeting factor XIIa for prophylactic use in adults and children aged 12 and older. This therapy, developed by CSL, offers once-monthly dosing via a subcutaneous autoinjector. In clinical trials, garadacimab-gxii demonstrated remarkable efficacy, with 62% of treated patients remaining attack-free and showing reductions of greater than 99% in overall HAE attacks compared with placebo.
On July 7, 2025, KalVista Pharmaceuticals announced the FDA’s approval of sebetralstat, the first oral, on-demand therapy for acute attacks in patients aged 12 and older. In clinical trials, patients experienced a median time from attack onset to treatment of just four minutes, with symptom relief beginning within approximately 1.79 hours.
The third treatment approved in this wave, donidalorsen, was announced by Ionis Pharmaceuticals on August 21, 2025. This RNA-targeted medicine is designed to prevent HAE attacks in adults and children aged 12 and older. Data from pivotal trials indicated that donidalorsen significantly reduced monthly attack rates by 81% and showed a 96% mean reduction in attacks over three years in patients previously on prophylactic therapies.
Dr. Raffi Tachdjian from UCLA Health expressed pride in these advancements, stating, “In the span of just three months, there were three new treatment modalities approved in HAE, which is mind-blowing.” He highlighted the progress made in the last two decades, stating that modern treatments for HAE began approximately 16 years ago.
Addressing Gaps in HAE Treatment for Younger Patients
Despite these developments, experts like Dr. Soteres and Dr. Michael Manning, an allergy and asthma specialist in Arizona, stress the need for treatments specifically indicated for children under 12 years old. Dr. Manning noted that “HAE is really a disease of childhood,” as 85% of patients develop symptoms before turning 20.
The conversation surrounding treatment accessibility also includes addressing the needs of patients living in rural areas and those who prefer not to take frequent injections or daily pills. As the landscape of HAE treatment continues to evolve, there is optimism about the potential for more options to emerge, allowing for better management of this challenging condition.
The recent approvals of garadacimab-gxii, sebetralstat, and donidalorsen reflect a field that is gaining momentum. The advances in treatment options are not only welcomed by healthcare providers but also offer hope to patients seeking effective management of their condition. As Dr. Manning humorously remarked, “We joke a little bit that there’s going to be more HAE drugs than patients out there.” The ongoing research and development signify a promising future for those affected by hereditary angioedema.