FDA accepts deucrictibant IR application for on-demand treatment of hereditary angioedema attacks

The FDA has accepted a New Drug Application (NDA) for deucrictibant immediate-release (IR) capsules, an investigational oral bradykinin B2 receptor antagonist for the on-demand treatment of hereditary angioedema (HAE) attacks in patients aged 12 years and older.¹ The agency set a Prescription Drug User Fee Act (PDUFA) target action date of April 23, 2027, for the application from Pharvaris N.V.¹

“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, CEO of Pharvaris.¹ Modig noted that treatment with deucrictibant IR in clinical studies resulted in rapid onset of symptom relief and accelerated resolution of attacks.¹

RAPIDe-3 trial design and efficacy results in hereditary angioedema

The NDA is supported by the global, placebo-controlled Phase 3 RAPIDe-3 trial (NCT06343779), which enrolled patients 12 years and older with HAE, including those with the normal C1 inhibitor subtype.² The study met its primary endpoint and all 11 secondary efficacy endpoints with statistical significance.¹ Across the development program, deucrictibant IR has been evaluated in the treatment of more than 1300 HAE attacks.¹ In RAPIDe-3, the median time to onset of symptom relief was 1.28 hours, the median time to a prespecified End of Progression measure was 17.48 minutes, and the median time to complete resolution of attack symptoms was 11.95 hours.¹ The sponsor reported a well-tolerated safety profile, though detailed adverse event rates have not yet been published in a peer-reviewed journal.¹

Disease burden and current on-demand treatment landscape for HAE

HAE is a rare, autosomal-dominant disorder driven by deficiency or dysfunction of the C1 esterase inhibitor protein, leading to unregulated bradykinin generation and recurrent, potentially life-threatening swelling of the skin, larynx, and gastrointestinal tract.³ Guidelines recommend treating attacks as early as possible to limit progression. Until 2025, all approved on-demand therapies—icatibant, ecallantide, and C1 inhibitor concentrates—required subcutaneous or intravenous administration.³ Sebetralstat, an oral plasma kallikrein inhibitor, became the first oral on-demand HAE therapy when it was FDA approved in July 2025.⁴ Deucrictibant IR, if approved, would be the first oral on-demand option that works through B2 receptor antagonism specifically, a mechanism with a longer clinical track record in HAE via injectable icatibant.³

Deucrictibant mechanism and Pharvaris’s bradykinin B2 antagonist pipeline

Deucrictibant is a small-molecule, orally bioavailable antagonist of the bradykinin B2 receptor, the same target as icatibant, and is designed to block bradykinin signaling that drives vascular permeability during an attack.¹ Pharvaris is separately developing an extended-release tablet formulation of deucrictibant intended for long-term prophylaxis, distinct from the immediate-release capsule under FDA review for acute, on-demand use.¹ The FDA granted deucrictibant orphan drug designation in 2022; the European Commission and Swissmedic have granted similar designations.¹

Clinical interpretation and next steps

NDA acceptance confirms the application is complete for substantive review but does not indicate the FDA’s eventual decision. Full efficacy and safety data from RAPIDe-3 have not yet appeared in a peer-reviewed publication, and cross-trial comparisons with sebetralstat or icatibant should be interpreted cautiously given differing trial designs and populations. Real-world data on durability of response, use in patients with laryngeal attacks, and long-term tolerability will help clinicians position deucrictibant IR relative to existing on-demand options as the April 2027 PDUFA date approaches.

References

1. Pharvaris N.V. Pharvaris announces FDA acceptance of New Drug Application for deucrictibant IR for on-demand treatment of hereditary angioedema attacks. News release. GlobeNewswire; July 6, 2026. Accessed 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

2. A study of deucrictibant to treat angioedema attacks in participants with hereditary angioedema (RAPIDe-3). ClinicalTrials.gov identifier: NCT06343779. Accessed July 6, 2026. https://clinicaltrials.gov/study/NCT06343779

3. Bork K, Aygören-Pürsün E, et al. Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema. N Engl J Med. 2010;363(6):532-541. doi:10.1056/NEJMoa0906393

4. KalVista Pharmaceuticals. KalVista Pharmaceuticals announces FDA approval of EKTERLY (sebetralstat), first and only oral on-demand treatment for hereditary angioedema. News release. July 7, 2025. Accessed July 6, 2026. https://ir.kalvista.com/news-releases/news-release-details/kalvista-pharmaceuticals-announces-fda-approval-ekterlyr