New HAE therapy delivers quicker relief in Phase 3 on-demand study
Most improved within hours, with fewer attacks needing extra treatment
On-demand treatment with deucrictibant can help resolve swelling attacks in people with all major forms of hereditary angioedema (HAE), according to top-line data from a Phase 3 clinical trial.
Pharvaris, deucrictibant’s developer, plans to use the Phase 3 findings to support a U.S. Food and Drug Administration (FDA) application for on-demand treatment of acute HAE attacks. The company said it is on track to submit its application to the FDA in the first half of 2026.
“These clinically meaningful and statistically significant results demonstrate deucrictibant’s early-onset treatment response, fast symptom relief and resolution, and well-tolerated safety profile,” Peng Lu, MD, PhD, chief medical officer of Pharvaris, said in a company press release. “This is an important step toward realizing deucrictibant’s potential to offer control of bradykinin-mediated angioedema attacks. With these data in hand, our team is working diligently to prepare for regulatory filings to enable access to this promising therapy.”
Understanding what drives HAE attacks
HAE is caused by mutations that lead to too much bradykinin, a signaling molecule that triggers swelling attacks. The most common forms, types 1 and 2, result from mutations in the SERPING1 gene. Type 3 HAE refers to rarer cases associated with mutations in other genes.
Deucrictibant is an oral therapy designed to block the B2 receptor, the pathway bradykinin uses to trigger swelling. By blocking the receptor, the therapy aims to interrupt the process and help reduce swelling during an attack.
“Bradykinin B2 receptor antagonism is a proven and effective mechanism for treatment of bradykinin-mediated angioedema. Injectable and oral on-demand therapies for HAE are available, however unmet medical needs remain. Effective, well-tolerated, and convenient acute treatment is an essential part of all HAE management plans due to unpredictable angioedema symptoms,” said Marc A. Riedl, MD, a professor at the University of California San Diego.
The new data come from a Phase 3 study called RAPIDe-3 (NCT06343779), which tested an immediate-release formulation of deucrictibant against a placebo as an on-demand treatment for people with HAE (ages 12 and older). The study’s main goal was to measure the median time to treatment response, defined as patients saying their symptoms felt at least “a little better.”
“I would like to sincerely thank the clinical study participants and their caregivers, the site investigators and staff, our study partners, the HAE community, and the Pharvaris team for their contributions to the RAPIDe-3 study,” Lu said. “Together, we carefully designed and rigorously executed a study evaluating deucrictibant’s ability to effectively address the unmet needs and high expectations of physicians, regulators, payers, and, most importantly, people living with HAE.”
Phase 3 study shows faster relief with treatment
Results showed that participants taking on-demand deucrictibant had a median time to symptom response of about 1.3 hours, with most people reporting noticeable relief within three hours and a median time to complete resolution of about 12 hours. For those given a placebo, the median time to any symptom relief was more than 12 hours, and the median time to full resolution was more than a day.
The median time to end of progression, the point when symptoms stop worsening, was also significantly shorter with deucrictibant — less than 20 minutes versus nearly four hours for placebo. Additional data showed that 83% of attacks needed only one immediate-release capsule, and fewer than 7% required any extra medication to get symptoms under control.
Effective, well-tolerated, and convenient acute treatment is an essential part of all HAE management plans due to unpredictable angioedema symptoms.
The efficacy of deucrictibant was consistent across people with HAE types 1, 2, and 3, according to Pharvaris.
“The comprehensive and compelling outcomes of RAPIDe-3, specifically the fast treatment response and early complete symptom resolution, demonstrate the potential benefits of deucrictibant as an important on-demand treatment for people living with HAE,” said Riedl, who was principal investigator in the RAPIDe-3 study.
Deucrictibant was overall well tolerated in the RAPIDe-3 study. No serious side effects related to the treatment were reported, and no participants withdrew because of safety issues.
Additional trials explore long-term prevention
Pharvaris is also running a Phase 3 study called CHAPTER-3 (NCT06669754), which is testing an extended-release formulation of deucrictibant as a potential preventive treatment to help reduce the risk of swelling attacks in HAE. The trial is recruiting participants at sites worldwide.
The company also recently announced plans for a study of the therapy in people with acquired angioedema.
“If the CHAPTER-3 pivotal Phase 3 study confirms deucrictibant extended-release tablet as a long-term prophylactic of HAE attacks, deucrictibant could be the first and only oral therapy to offer control in both the on-demand and prophylactic treatment of bradykinin-mediated angioedema attacks,” said Berndt Modig, CEO of Pharvaris.
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