The landscape for managing hereditary angioedema (HAE) has shifted significantly in 2025, with the US Food and Drug Administration (FDA) approving three new treatments within a span of just three months. The drugs—garadacimab-gxii (Andembry), sebetralstat (Ekterly), and donidalorsen (Dawnzera)—promise to enhance patient care for a disease often plagued by delayed diagnosis and treatment.
The first approval came on June 16, 2025, when the FDA cleared garadacimab-gxii, a groundbreaking therapy targeting factor XIIa, for the prevention of HAE attacks in adults and children aged 12 years and older. Developed by CSL, this treatment is noteworthy for its once-monthly dosing, administered via a citrate-free, subcutaneous autoinjector. Data from the phase 3 VANGUARD trial revealed that 62% of patients remained attack-free, demonstrating a substantial reduction in overall HAE attacks.
In July, KalVista Pharmaceuticals announced the FDA approval of sebetralstat, marking it as the first oral, on-demand therapy for treating acute HAE attacks in patients aged 12 years and older. The results from clinical trials showed that symptom relief began within approximately 1.79 hours, with significant improvements in severity and complete resolution occurring within hours. This rapid response could redefine how acute attacks are managed.
The third treatment, donidalorsen, received FDA approval on August 21, 2025. This RNA-targeted medicine, developed by Ionis Pharmaceuticals, aims to prevent HAE attacks in similar age groups. Clinical trial data indicated a remarkable mean reduction of 96% in HAE attacks over three years, further highlighting the potential for enhanced disease control.
According to Daniel Soteres, MD, PhD, from the University of Colorado Health Sciences Center, the introduction of multiple treatment options is crucial. “Every patient has an individual set of values, an individual health literacy,” he stated. “Their needs change over time.” This sentiment underscores the importance of personalized medicine in managing HAE, a rare genetic condition that affects an estimated 1 in 50,000 people globally, including approximately 6,000 in the United States.
HAE can result in life-threatening swelling attacks in various body parts, including the face, throat, and abdomen. Diagnosing the condition can be challenging, as its symptoms frequently overlap with other forms of angioedema. A report published in May 2025 highlighted that up to 90% of HAE-related deaths occur in undiagnosed patients who experience asphyxiation during attacks.
Growing Understanding of HAE and Its Impact
At the 2025 American College of Allergy, Asthma, & Immunology (ACAAI) Annual Scientific Meeting held in Orlando, Florida, experts discussed the significant burden HAE places on patients. Soteres noted that children with HAE often encounter delayed or inconsistent emergency care, leading to long-term negative perceptions of their condition. Another study emphasized that the impact of HAE extends beyond immediate health concerns, often resulting in missed school days and academic challenges.
Prior to June 2025, there were nine FDA-approved treatments for HAE, including both preventive and acute therapies. These included berotralstat (Orladeyo), lanadelumab-flyo (Takhzyro), and several C1 esterase inhibitors. The newly approved treatments bring the total to twelve, providing a broader array of options for personalized treatment plans.
The newer therapies not only act earlier in the HAE pathway but also offer novel routes of administration or utilize innovative molecular mechanisms. “In the span of just three months, there were three new treatment modalities approved in HAE,” said Raffi Tachdjian, MD, MPH, from UCLA Health. He added that this rapid advancement is a testament to the progress made in the field over the past two decades.
Future Directions and Unmet Needs
Despite the progress, experts pointed out that the need for effective treatments for children under 12 remains a significant gap. Soteres remarked, “The burden of these attacks on children has previously been considered more of an issue beginning at the onset of puberty, but reports indicate that attacks can start as early as 2 years old.”
Similarly, Michael Manning, MD, an allergy and immunology specialist in Arizona, emphasized that HAE primarily affects children, with 85% of patients developing symptoms before the age of 20. The limited treatment options for younger patients highlight a critical unmet need in the management of HAE.
Experts also called for further research to improve treatment portability and address gaps in care for rural populations, those who have aversions to frequent injections, and patients who prefer not to take daily medications.
The approvals of garadacimab-gxii, sebetralstat, and donidalorsen herald a promising era in HAE treatment, with the potential for more personalized and effective management strategies. As Manning humorously noted, “We joke a little bit that there’s going to be more HAE drugs than patients out there.” This optimism reflects the ongoing commitment to advancing understanding and treatment of this challenging condition.
