Pharvaris Reports Positive Phase 3 Results for Oral HAE Treatment Deucrictibant
核心洞察
Pharvaris announced positive topline data from its RAPIDe-3 pivotal Phase 3 study, with deucrictibant achieving median time to symptom relief in 1.28 hours versus over 12 hours for placebo.
The global study enrolled 134 participants across 24 countries, representing the most diverse patient population in an on-demand HAE (搜索) trial, with efficacy consistent across all HAE subtypes.
All secondary efficacy endpoints were met, including End of Progression at 17.47 minutes and complete symptom resolution at 11.95 hours, with no treatment-related serious adverse events.
Pharvaris has announced positive topline data from its RAPIDe-3 pivotal Phase 3 study, confirming the potential of deucrictibant as an oral on-demand treatment for hereditary angioedema (搜索) (HAE (搜索)) attacks. The trial met its primary endpoint with a median time to onset of symptom relief achieved in 1.28 hours, significantly faster than placebo (p<0.0001).
Study Design and Patient Population
The RAPIDe-3 global Phase 3, placebo-controlled study evaluated orally administered deucrictibant immediate-release capsule (20 mg) for the on-demand treatment of attacks in people 12 years and older with HAE (搜索). The study enrolled a total of 134 participants from 24 countries on six continents, representing the most diverse patient population yet in an on-demand HAE trial.
The patient population included adolescents and adults, participants on and not on long-term prophylaxis, people with HAE (搜索) type 1, HAE type 2, and HAE with normal C1 inhibitor, and attacks of varying severities across all body locations. This makes the RAPIDe-3 study the first-ever on-demand HAE study to be fully compliant with the Core Outcome Set recommended in the AURORA consensus.
Efficacy Results
All secondary efficacy endpoints were met, including End of Progression at 17.47 minutes compared to 228.67 minutes for placebo (p<0.0001) and complete symptom resolution at 11.95 hours versus over 24 hours for placebo (p<0.0001). The primary endpoint and all 11 secondary efficacy endpoints achieved statistical significance under a multiplicity-control procedure.
Compared to placebo, deucrictibant demonstrated compelling efficacy across multiple measures:
- Time to substantial symptom relief by Patient Global Impression of Change at least "better": 2.85 hours versus over 12 hours (p<0.0001)
- Time to substantial symptom relief by Patient Global Impression of Severity ≥1-level improvement: 2.41 hours versus over 12 hours (p<0.0001)
- 83.0% of attacks were treated with a single capsule of deucrictibant
- 93.2% of deucrictibant-treated attacks were treated without use of rescue medication
Results showed efficacy and safety outcomes consistent across all HAE (搜索) subtypes and attack severities.
Safety Profile
Deucrictibant was well tolerated, with no treatment-related serious adverse events and no discontinuations due to side effects. The safety and tolerability profile was consistent with completed and ongoing studies of deucrictibant for the treatment of HAE (搜索) attacks with no safety signals identified.
Expert Commentary
Marc A. Riedl, Professor of Medicine at UC San Diego and principal investigator, commented: "Bradykinin B2 receptor (搜索) antagonism is a proven and effective mechanism for treatment of bradykinin-mediated angioedema (搜索). Injectable and oral on-demand therapies for HAE (搜索) 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."
He added: "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 (搜索)."
Company Perspective
Peng Lu, Chief Medical Officer of Pharvaris, stated: "These clinically meaningful and statistically significant results demonstrate deucrictibant's early-onset treatment response, fast symptom relief and resolution, and well-tolerated safety profile. This is an important step toward realizing deucrictibant's potential to offer control of bradykinin-mediated angioedema (搜索) attacks."
Berndt Modig, CEO of Pharvaris, added: "Deucrictibant combines the proven and effective mechanism of bradykinin B2 receptor (搜索) antagonism in HAE (搜索) with the convenience of oral administration. We are thrilled that RAPIDe-3 confirmed the profile of deucrictibant IR capsule established in Phase 2."
Regulatory Timeline
Pharvaris remains on track to submit a New Drug Application with the U.S. Food and Drug Administration in the first half of 2026 for the on-demand treatment of acute attacks of HAE (搜索). The data from this first pivotal Phase 3 study will serve as the basis for marketing authorization applications.
About Deucrictibant
Deucrictibant is a novel, potent, orally bioavailable small-molecule bradykinin B2 receptor (搜索) antagonist currently in clinical development. Pharvaris is developing two formulations for oral administration: an extended-release tablet for prophylactic treatment and an immediate-release capsule for on-demand treatment. Deucrictibant has been granted orphan drug designation for the treatment of bradykinin-mediated angioedema (搜索) by the U.S. Food and Drug Administration, the European Commission, and Swissmedic.