Pharvaris: Positive pivotal study data for treatment of hereditary angioedema attacks

Pharvaris (Nasdaq: PHVS), a late-stage biopharmaceutical company developing novel, oral bradykinin B2 receptor antagonists to help address unmet needs of those living with bradykinin-mediated diseases such as hereditary angioedema (HAE) and acquired angioedema due to C1 inhibitor deficiency (AAE-C1INH), today announced RAPIDe-3 pivotal data confirming the potential of deucrictibant’s differentiated profile for the on-demand treatment of HAE attacks. The data from Pharvaris’ first pivotal Phase 3 study will serve as the basis for marketing authorization applications, which are planned to be filed starting in the first half of 2026.

RAPIDe-3 Study Design and Results
The RAPIDe-3 (NCT06343779) global Phase 3, placebo-controlled study evaluated orally administered deucrictibant immediate-release (IR) capsule (20 mg) for the on-demand treatment of attacks in people 12 years and older with HAE. The study enrolled a total of 134 participants from 24 countries on six continents. The patient population studied included adolescents and adults; participants on and not on long-term prophylaxis (LTP); people with HAE type 1, HAE type 2, and HAE with normal C1 inhibitor; and attacks studied included those of varying severities and across all body locations. This makes this participant population the most representative and, based on prespecified endpoints, 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. The primary endpoint and all 11 secondary efficacy endpoints, assessed sequentially under a multiplicity-control procedure, achieved statistical significance.

Compared to placebo, deucrictibant demonstrated compelling and differentiating efficacy:

• Faster median time to onset of treatment response:
  • Time to onset of symptom relief by PGI-C3 at least “a little better”: 1.28 hours versus >12 hours (p<0.0001)
  • Time to End of Progression: 17.47 minutes versus 228.67 minutes (p<0.0001)
• Shorter median time to substantial symptom relief:
  • Time to substantial symptom relief by PGI-C at least “better”: 2.85 hours versus >12 hours (p<0.0001)
  • Time to substantial symptom relief by PGI-S4 ≥1-level improvement: 2.41 hours versus >12 hours (p<0.0001)
• Earlier complete symptom resolution:
  • Median time to complete symptom resolution by PGI-S “none”: 11.95 hours versus >24 hours (p<0.0001)
• Fewer attacks treated with second dose or rescue medication within 12 hours:
  • 83.0% of attacks were treated with a single capsule of deucrictibant IR
  • 93.2% of deucrictibant-treated attacks were treated without use of rescue medication

Marc A. Riedl, M.D., M.S., Professor of Medicine, Clinical Director of the U.S. Hereditary Angioedema Association (HAEA) Angioedema Center at the University of California San Diego (UCSD), and principal investigator in the RAPIDe-3 study, commented, “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. 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.”

Peng Lu, M.D., Ph.D., Chief Medical Officer of Pharvaris, stated, “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. 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.”

Dr. Lu continued, “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 attacks. With these data in hand, our team is working diligently to prepare for regulatory filings to enable access to this promising therapy.”

Berndt Modig, Chief Executive Officer of Pharvaris, added, “Since its founding, Pharvaris has spent the last decade pioneering science for patient choice. Deucrictibant combines the proven and effective mechanism of bradykinin B2 receptor antagonism in HAE with the convenience of oral administration. We are thrilled that RAPIDe-3 confirmed the profile of deucrictibant IR capsule established in Phase 2. 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.”

In RAPIDe-3, deucrictibant was well tolerated with no treatment-related serious adverse events and no participants discontinuing treatment due to treatment-emergent adverse events. To date, the safety and tolerability profile was consistent with completed and ongoing studies of deucrictibant for the treatment of HAE attacks with no safety signals identified.

An open-label extension of deucrictibant for the on-demand treatment of HAE attacks, RAPIDe-2 Part B, is ongoing.

Pharvaris plans to present additional efficacy, safety, and patient experience data at upcoming medical congresses.

Pharvaris remains on track to submit a New Drug Application (NDA) with the U.S. Food and Drug Administration (FDA) in the first half of 2026 for the on-demand treatment of acute attacks of HAE.

References

• Petersen RS, et al. A Core Outcome Set for Efficacy of Acute Treatment of Hereditary Angioedema. J Allergy Clin Immunol Pract. 2024;12(6):1614-1621. doi:10.1016/j.jaip.2024.04.007.
• PGI-C: Patient Global Impression of Change
• PGI-S: Patient Global Impression of Severity