Pharvaris moves toward FDA filing for fast-acting deucrictibant for HAE
Developer to soon seek approval of on-demand treatment for swelling attacks
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Pharvaris plans to soon submit an application to the U.S. Food and Drug Administration (FDA) seeking approval of its immediate-release formulation of deucrictibant for on-demand treatment of hereditary angioedema (HAE) swelling attacks.
The company said it’s on track to file with the regulatory agency by the end of June — a submission supported by recent data from a Phase 3 clinical trial, dubbed RAPIDe-3 (NCT06343779), that demonstrated the oral therapy’s effectiveness in reducing overall HAE attack duration.
Further, those data showed that deucrictibant began relieving HAE symptoms within a mean of 1.3 hours, compared with 12 hours with a placebo.
The developer also announced, in a company press release detailing first-quarter financial results and providing a business update, that it expects topline data from the pivotal CHAPTER-3 clinical trial (NCT06669754) later this year. That Phase 3 trial is testing the safety and effectiveness of once-daily dosing with the extended-release formulation of deucrictibant to prevent swelling attacks in people ages 12 and older with HAE.
In addition, enrollment is ongoing at sites in the U.S. and Europe of an estimated 32 adults with acquired angioedema (AAE) in the Phase 3 CREAATE trial (NCT07266805).
“In 2026, Pharvaris remains focused on execution across our late-stage programs, including reporting CHAPTER-3 data in the third quarter and enrolling in CREAATE, and on establishing our commercial infrastructure in preparation for the potential launch of deucrictibant IR,” said Berndt Modig, Pharvaris’ CEO.
Angioedema is characterized by episodes of swelling that occur when fluid builds up in the deeper layers of the skin or mucous membranes. In HAE, this is caused by genetic mutations that lead to the overproduction of bradykinin, a protein that widens blood vessels and causes fluid to leak into surrounding tissues.
Unlike HAE, acquired angioedema usually results from an underlying disorder, such as certain cancers or autoimmune diseases, that impairs the function of C1-INH, a protein that regulates bradykinin production.
Deucrictibant, formerly known as PHA121, is an oral small molecule designed to block the B2 bradykinin receptor, preventing bradykinin from interacting with the receptor and triggering blood vessel leakage. It’s available as immediate-release capsules that reach therapeutic exposure within 15-30 minutes for on-demand treatment, and as extended-release tablets that maintain exposure over 24 hours, allowing once-daily dosing to prevent swelling attacks.
Deucrictibant shown effective for treating and preventing HAE attacks
The therapy is now being tested for AAE in CREAATE, a small clinical trial that’s enrolling adults at 17 sites in the U.S. and Europe. Eligible participants will have AAE due to C1-inhibitor (C1-INH) deficiency.
In multiple clinical trials for HAE, deucrictibant has shown positive results for both the treatment and prevention of swelling attacks.
In the Phase 2 RAPIDe-1 study (NCT04618211), the on-demand formulation outperformed a placebo, with most attacks resolving within 30 minutes. Long-term data from the RAPIDe-2 (NCT05396105) extension study further showed sustained effectiveness, with nearly all attacks achieving symptom relief within 12 hours and complete resolution within 24 hours.
For preventive treatment, the Phase 2 CHAPTER-1 trial (NCT05047185) demonstrated a significant reduction in swelling attacks versus a placebo, with attack rates reduced by 92% after nearly three years in the ongoing extension study. The Phase 3 CHAPTER-3 trial, meanwhile, evaluated the once-daily extended-release formulation. The long-term CHAPTER-4 (NCT06679881) extension study is continuing at sites worldwide.
In both the U.S. and the European Union, deucrictibant has been granted orphan drug status for the treatment of bradykinin-mediated angioedema. This designation aims to incentivize companies to develop therapies for rare diseases by offering incentives like tax credits, fee waivers, and a period of market exclusivity if the treatment is ultimately approved.
