FDA Accepts NDA for Oral Deucrictibant for HAE Attacks

The US Food & Drug Administration (FDA) has accepted Pharvaris' New Drug Application (NDA) for deucrictibant immediate-release (IR) capsules, an oral bradykinin B2 receptor antagonist intended for on-demand treatment of hereditary angioedema (HAE) attacks, with a Prescription Drug User Fee Act (PDUFA) target action date of April 23, 2027.¹ If approved, deucrictibant IR would become the first oral agent in its drug class for acute HAE attack treatment.

The submission is supported by data from the phase 3 RAPIDe-3 trial, a global, randomized, double-blind, placebo-controlled, crossover study evaluating deucrictibant IR in patients aged ≥ 12 years with HAE, including those with normal C1 inhibitor levels.2 According to Pharvaris, the trial met its primary endpoint and all 11 secondary efficacy endpoints with statistical significance.¹ Reported median times were 1.28 hours to onset of symptom relief, 17.48 minutes to end of progression, and 11.95 hours to complete resolution of attack symptoms.¹

The company describes the safety profile as well tolerated, though granular adverse event rates and comparator data have not yet been published in a peer-reviewed format. The NDA package reportedly draws on treatment data from > 1300 HAE attacks across the deucrictibant development program.¹

HAE is a rare genetic disorder, with an estimated prevalence of approximately 1 in 50,000 people worldwide, caused most often by C1 inhibitor deficiency that leads to excess bradykinin generation and episodic, potentially life-threatening swelling of the skin, gastrointestinal tract, and upper airway.³ Current on-demand options include plasma-derived and recombinant C1 inhibitor concentrates, the subcutaneous B2 antagonist icatibant, and the plasma kallikrein inhibitor ecallantide, most of which require injection or infusion.4 Sebetralstat, an oral kallikrein inhibitor, was approved in 2025 as the first oral on-demand HAE therapy, based on the phase 3 KONFIDENT trial.5 An oral B2 antagonist would offer a different mechanism within the same “oral on-demand” category rather than a first-in-kind route of administration.

Deucrictibant works by blocking bradykinin signaling at the B2 receptor, the same target validated by icatibant, but is formulated for oral absorption rather than injection.¹ Pharvaris is also developing an extended-release tablet formulation of the same molecule for long-term prophylaxis, currently in phase 3 testing (CHAPTER-3, NCT06669754). The FDA granted deucrictibant orphan drug designation in 2022, a status also conferred by the European Commission and Swissmedic.¹

For prescribers, the reported symptom-relief and resolution times are similar in magnitude to those described for sebetralstat and for icatibant in prior trials, though cross-trial comparisons are limited by differences in study design, endpoint definitions, and patient populations.4 The clinical value of an oral B2 antagonist will depend on how it performs against these existing options in practice, including in patients who do not respond adequately to kallikrein inhibition, and on longer-term safety data as more patients are exposed.

“After 10 years of dedicated effort by the team at Pharvaris, this FDA acceptance of deucrictibant IR’s NDA represents a major milestone in our journey to develop a differentiated therapy with the potential to improve the standard of care for people living with HAE,” said Berndt Modig, chief executive officer of Pharvaris, in a statement.1 “By leveraging this trusted mechanism and its chemical properties, deucrictibant IR has the potential to be an oral on-demand medicine that addresses unmet needs of those living with HAE.”

References

Pharvaris N.V. Pharvaris announces FDA acceptance of New Drug Application for deucrictibant IR for on-demand treatment of hereditary angioedema attacks. GlobeNewswire. July 6, 2026. https://www.globenewswire.com/news-release/2026/07/06/3322293/0/en/pharvaris-announces-fda-acceptance-of-new-drug-application-for-deucrictibant-ir-for-on-demand-treatment-of-hereditary-angioedema-attacks.html

ClinicalTrials.gov. Study of oral deucrictibant soft capsule for on-demand treatment of angioedema attacks in adolescents and adults with hereditary angioedema. NCT06343779. Updated 2026. https://clinicaltrials.gov/study/NCT06343779

Jones D, Narsipur N, Wade SW, et al. Patient-reported disease burden and health care utilization of HAE-nl-C1INH: insights from a real-world survey. Clin Exp Med. 2026;26(1):108. Published 2026 Jan 14. doi:10.1007/s10238-025-02010-5

Li HH, Aygören-Pürsün E, Magerl M, et al. Indirect treatment comparison of oral sebetralstat and intravenous recombinant human C1 esterase inhibitor for on-demand treatment of hereditary angioedema attacks. Allergy Asthma Clin Immunol. 2025;21:19. doi:10.1186/s13223-025-00955-6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11909897/

Johnson V. Sebetralstat FDA-Approved as First Oral, On-Demand for Hereditary Angioedema. HCPLive. Published on July 7, 2025. Accessed on July 6, 2026. https://www.hcplive.com/view/sebetralstat-fda-approved-as-first-oral-on-demand-for-hereditary-angioedema