An Oral Drug Shows Long-Term Promise for a Rare Form of Autoimmune Angioedema
Autoimmune angioedema is a broad term for swelling disorders in which the immune system plays a central role, and one of the rarest and most difficult-to-treat subtypes is acquired angioedema due to C1-inhibitor deficiency, often abbreviated as AAE-C1-INH. Unlike hereditary angioedema (HAE), which results from a genetic mutation, acquired forms typically develop in adulthood and arise when the body begins producing antibodies that consume or block C1 inhibitor, a protein that normally keeps inflammatory and bradykinin-producing pathways in check. When C1 inhibitor levels drop, excessive bradykinin accumulates, triggering episodes of sudden, severe swelling in the face, throat, limbs, and gastrointestinal tract. The swelling can be life-threatening, particularly when it affects the airway, and attacks may be unpredictable and frequent. The condition affects roughly one in every 500,000 people, often in association with underlying lymphoproliferative disorders or other autoimmune conditions, though it can also occur without a clear trigger.
Despite how disruptive and dangerous these attacks can be, there are currently no therapies approved by the FDA specifically to prevent episodes of AAE-C1-INH. Icatibant, a bradykinin B2 receptor antagonist given by injection, can treat acute attacks when they occur, but it is used off-label for this condition and does not provide ongoing protection. This gap has left many patients cycling through repeated emergency interventions without a reliable way to reduce how often those emergencies happen.
A study published in December 2025 in the Journal of Allergy and Clinical Immunology offers some of the most encouraging long-term evidence to date. Researchers led by Danny M. Cohn, MD, PhD, and colleagues at a Dutch academic center reported results from patients treated with deucrictibant, an oral bradykinin B2 receptor antagonist developed by Pharvaris, as long-term prophylaxis for AAE-C1-INH. The study extended prior findings from a randomized controlled trial that had shown deucrictibant reduced monthly attack rates to zero across all patients during the treatment period, compared to rates of one to two attacks per month on placebo.
Deucrictibant works by blocking the receptor through which bradykinin triggers swelling, preventing attacks from escalating even when C1 inhibitor levels are low. Being an oral medication is a meaningful practical advantage; many current options for managing angioedema require intravenous or subcutaneous administration, which can be burdensome for patients and families. The oral formulation means patients could potentially take their preventive therapy at home, without infusions or injections.
Pharvaris is currently conducting CREAATE, a global Phase 3 trial evaluating deucrictibant for both acute and prophylactic treatment of AAE-C1-INH, building on the promising earlier findings. If successful, this would be the first drug approved for prevention of swelling attacks in acquired angioedema patients. The research represents an important step forward for a patient population that has long had to manage a serious and frightening condition without adequate preventive options.
Source: Journal of Allergy and Clinical Immunology, Volume 156, Issue 6, December 2025, Pages 1650-1655. Authors: Mats de Lange MD, Remy S. Petersen MD PhD, Lauré M. Fijen MD PhD, Danny M. Cohn MD PhD. DOI: 10.1016/j.jaci.2025.07.033. URL: https://www.sciencedirect.com/science/article/pii/S0091674925008899
Disclaimer: This summary is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare provider for diagnosis and treatment decisions.