PHVS News & Events

Pharvaris announced that two articles have been published back-to-back in the same issue of The Lancet Haematology. The articles detail data from the two randomized Phase 2 studies, CHAPTER-1 and RAPIDe-1, evaluating the efficacy and safety of deucrictibant, a potent, orally bioavailable small-molecule bradykinin B2 receptor antagonist, in development for the prophylaxis and on-demand treatment of HAE attacks, respectively. "Since HAE is a bradykinin-mediated disease, regulation of bradykinin signaling through B2 receptor antagonism could both prevent HAE attacks and manage angioedema symptoms when they occur," said Marc Riedl, Professor of Medicine, Clinical Director of the U.S. Hereditary Angioedema Association Angioedema Center at the University of California San Diego. "The statistically significant, placebo-controlled data from these two distinct clinical studies provide important evidence that deucrictibant, a bradykinin B2 receptor antagonist, may offer a viable option for both prophylactic and acute treatment of HAE attacks. Based on these results, deucrictibant is emerging as a potentially unique oral therapy for HAE, providing on-demand and preventative treatment effects through the availability of both the immediate-release capsule and extended-release tablet. This complementary approach may further improve HAE management for patients and prescribers alike." CHAPTER-1, a double-blind, placebo-controlled Phase 2 proof-of-concept study of deucrictibant for the prophylactic treatment of HAE attacks, demonstrated statistically significant reduction in the occurrence of attacks and clinically meaningful improvements in disease control and health-related quality of life. Deucrictibant was well tolerated at both doses tested. RAPIDe-1, a double-blind, placebo-controlled Phase 2 study of deucrictibant immediate-release capsule for the on-demand treatment of HAE attacks, demonstrated a statistically significant reduction in severity of attack manifestations, as well as a reduced time to symptom relief and resolution. Deucrictibant was well tolerated at all doses tested. Topline data from CHAPTER-3, an ongoing Phase 3 clinical study evaluating deucrictibant extended-release tablet for the prophylactic treatment of HAE attacks, is anticipated in the third quarter of 2026. Topline data from RAPIDe-3, a pivotal, placebo-controlled Phase 3 clinical study evaluating deucrictibant immediate-release capsule for the on-demand treatment of HAE attacks, demonstrated that treatment with deucrictibant resulted in faster symptom relief and complete symptom resolution of HAE attacks and in most attacks being treated with a single capsule.

Pharvaris announced that results from a Pharvaris-sponsored non-interventional, mixed methods, real-world study assessing the patient experience during acute HAE attacks across alternative endpoints used in clinical studies have been published in Clinical Reviews in Allergy & Immunology. The study evaluated the patient experience with HAE attack manifestations, and what constitutes meaningful changes in those manifestations, to support the inclusion of meaningful endpoints in clinical studies for on-demand treatment, or ODT, of HAE attacks, such as RAPIDe-3. Although approved medicines exist for the on-demand treatment of HAE attacks, there have been no head-to-head studies of on-demand therapies, and cross-trial comparisons have been challenging due to lack of uniformity in study design. Additionally, generation of evidence related to the key symptoms experienced by people during HAE attacks, insights into the subsequent perception from patients as to what are clinically-meaningful changes in symptoms, validation of the content of various patient-reported outcome, or PRO, instruments to support the evaluation of those symptoms, and confirmation of patient understanding and interpretation of that content, all could help in the evaluation of on-demand therapies by regulators, payers, and the HAE community. This mixed methods study provides strong evidence that the PGI and AMRA instruments are reliable, valid, and sensitive tools for assessing PROs in HAE attacks. Within the PRO assessments, most concepts were considered important by participants. Qualitative interviews confirmed that even relatively small improvements could be meaningful, such as the moment an attack was no longer worsening, as captured by the endpoint of End of Progression. Consistency across all PRO assessments of attack manifestation and response assessment were seen; End of Progression was the first-in-time achieved endpoint, followed by symptom relief, then symptom resolution. Importantly, the median time to onset of initial symptom relief as measured as PGI-C rating of at least "a little better" aligned more closely with the timing of AMRA-3 greater than or equal to20% than with the timing of AMRA-3 greater than or equal to30%. These results informed the hierarchy of endpoints in the Phase 3 RAPIDe-3 trial of deucrictibant and may also inform future trials of ODTs for HAE attacks.