Pharvaris advances first bradykinin B2 antagonist for on-demand HAE treatment to FDA review

Switzerland-based Pharvaris N.V. (Nasdaq: PHVS) [has submitted a New Drug Application](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) to the US FDA for [deucrictibant ](https://app.allsci.com/drugs/ASC-DR-0000000044860-1.0-1775585065)immediate-release (IR) capsule (20 mg) for the on-demand treatment of hereditary angioedema (HAE) attacks. If approved, deucrictibant would become the first oral bradykinin B2 receptor antagonist indicated for treating HAE attacks — a mechanistic distinction that sets it apart from the only currently approved oral on-demand therapy, sebetralstat (Ekterly), which targets plasma kallikrein. The FDA has assigned a PDUFA target action date of April 23, 2027. Pharvaris submitted the NDA for deucrictibant IR capsules seeking approval in patients 12 years and older with HAE, including those with HAE with normal C1 inhibitor, the company said. The filing covers a single 20 mg oral capsule dose for treatment of acute attacks. The NDA encompasses data from the treatment of over 1,300 HAE attacks across Pharvaris's clinical program, the company said. The pivotal evidence supporting the application comes from [RAPIDe-3](https://clinicaltrials.gov/study/NCT06343779), a global, randomized, placebo-controlled Phase III study evaluating deucrictibant IR in patients 12 years and older with HAE. The trial met its primary endpoint and all 11 secondary efficacy endpoints with statistical significance, the company reported. Results demonstrated a median time to onset of symptom relief of 1.28 hours with deucrictibant versus more than 12 hours with placebo, and a median time to complete resolution of attack symptoms of 11.95 hours versus more than 48 hours with placebo. The trial also introduced a novel endpoint, End of Progression, defined as the earliest timepoint at which symptoms stop worsening; the median time to this endpoint was 17.48 minutes with deucrictibant. Data presented at the European Academy of Allergy and Clinical Immunology Annual Congress 2026 showed that 83% of deucrictibant-treated attacks were managed with a single capsule, and 93.2% did not require conventional rescue medication. Deucrictibant demonstrated a well-tolerated safety profile with no treatment-related serious adverse events and no discontinuations due to treatment-emergent adverse events, the company said. Deucrictibant holds orphan drug designation from the US FDA, the European Commission, and Swissmedic. Deucrictibant is a small-molecule, orally bioavailable bradykinin B2 receptor antagonist that works by blocking bradykinin signaling, the downstream mediator of vascular permeability that drives HAE attacks. This mechanism is shared with icatibant, a subcutaneously administered B2 receptor antagonist already approved for HAE treatment, but deucrictibant is formulated for oral administration, which the company positions as a meaningful convenience advantage. The HAE treatment landscape has shifted substantially over the past year. KalVista Pharmaceuticals' sebetralstat (Ekterly), [approved by the US FDA in July 2025](https://app.allsci.com/news/ASC-NR-0000003849877-1.0-1782914439) and subsequently acquired by Chiesi Group, is the first and only approved oral on-demand therapy and operates through plasma kallikrein inhibition rather than B2 receptor blockade. Deucrictibant, if approved, would offer a second oral option acting at a different node in the bradykinin pathway. The HAE prophylaxis space has also seen recent entries, including CSL Behring's garadacimab (Andembry), approved in June 2025, and Ionis Pharmaceuticals' donidalorsen, approved in August 2025 as the first RNA-targeted prophylactic for HAE. Further disruption may come from Intellia Therapeutics (Nasdaq: NTLA), which [initiated a rolling BLA submission](https://app.allsci.com/news/ASC-NR-0000002367286-1.0-1779381220) for lonvoguran ziclumeran (lonvo-z), an in vivo CRISPR gene editing candidate targeting the KLKB1 gene, with a potential US launch targeted for the first half of 2027. For Pharvaris, the NDA acceptance marks the culmination of a development program built around the bradykinin B2 receptor as a therapeutic target. The company is also developing deucrictibant in an extended-release tablet formulation for prophylactic use, with topline data from the pivotal Phase III CHAPTER-3 study anticipated in Q3 2026. A separate Phase III program, CREAATE, is evaluating deucrictibant for both prophylactic and on-demand treatment of acquired angioedema due to C1 inhibitor deficiency. The dual-formulation strategy — immediate-release for acute attacks and extended-release for prevention — positions Pharvaris to potentially address both treatment settings with the same mechanism, and [data presented at EAACI 2026](https://app.allsci.com/news/ASC-NR-0000003831421-1.0-1781521570) suggested that combined use of the two formulations carries adequate safety margins for patients experiencing breakthrough attacks while on prophylaxis. The company said it has already begun building commercial infrastructure in anticipation of a potential approval. *** This article was generated with AI assistance and reviewed and edited by the AllSci editorial team Explore more at AllSci News: [https://allsci.com/news/](https://allsci.com/news/) --- Spot something wrong? 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