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 angioedema (AE-BK), such as hereditary angioedema (HAE) and acquired angioedema due to C1 inhibitor deficiency (AAE-C1INH), today announced statistically significant and clinically meaningful topline results of the CHAPTER-3 pivotal Phase 3 study evaluating deucrictibant extended-release (XR) tablet for the prevention of HAE attacks. The primary endpoint and all secondary efficacy endpoints were met with statistical significance. Data from the CHAPTER-3 study will serve as the basis for marketing authorization applications, which are planned to be submitted starting in the first half of 2027.

CHAPTER-3 Study Design and Results
The CHAPTER-3 (NCT06669754) global Phase 3, double-blind, placebo-controlled study evaluated orally administered deucrictibant XR tablet (40 mg, once daily) for the prevention of attacks in adolescents and adults with HAE. CHAPTER-3 is the first and only prophylaxis Phase 3 study to evaluate all three types of HAE, including people with HAE type 1, HAE type 2, or HAE with normal C1 inhibitor. The study randomized 85 participants from 21 countries in a 2:1 ratio to deucrictibant XR (N=55) or placebo (N=30) for 24 weeks of treatment.

Treatment with deucrictibant XR in participants with all types of HAE reduced the mean monthly attack rate by 83% (p<0.0001). Further analysis in the 80 participants with HAE Type 1 or Type 2 showed that the mean monthly attack rate was 87% lower in the deucrictibant XR group compared to placebo. Primary endpoint results were consistent across subgroups. All secondary efficacy endpoints, assessed sequentially under a multiplicity-control procedure, were also met with statistical significance. In CHAPTER-3, administration of deucrictibant XR resulted in early-onset protection within the first week, which was then sustained through the 24 weeks of study treatment. Robust reductions in attack rate from baseline and increases in the percentage of attack-free participants were observed in the deucrictibant-treated group.

In CHAPTER-3, deucrictibant XR was well tolerated with most treatment-emergent adverse events being mild or moderate. There were no treatment-related serious adverse events reported. One participant in each group discontinued treatment due to an adverse event.

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 CHAPTER-3 study, commented, “Alongside the RAPIDe-3 data in the on-demand setting, these CHAPTER-3 results further confirm the value of targeting the bradykinin B2 receptor for both the prevention and treatment of attacks across all types of HAE. People living with HAE are seeking novel treatment options that offer improved disease control and health-related quality of life, with reduced treatment burden. If approved, the efficacy, tolerability, and convenient oral administration position deucrictibant XR as a potential important addition to HAE clinical practice, supporting individualized treatment strategies designed around shared decision making.”

Peng Lu, M.D., Ph.D., President of Pharvaris, stated, “People living with HAE have been waiting for a well-tolerated oral therapy with injectable-like efficacy; we believe deucrictibant XR can help address this unmet need. CHAPTER-3 showed statistically significant reductions in attack frequency, characterized by early and sustained protection, clinically meaningful improvements in health-related quality of life, and better HAE control. The successful study completion would not have been possible without the incredible contributions of the clinical study participants and their caregivers, the site investigators and staff, the HAE community, our study partners, and the Pharvaris team, to whom we are sincerely thankful.”

Dr. Lu continued, “With the ongoing regulatory review of the NDA of deucrictibant IR for on-demand treatment of HAE attacks and the planned submission of an NDA for deucrictibant XR for prevention of bradykinin-mediated angioedema attacks, we are focused on commercial preparation for two potential launches. Pharvaris aims to set a new standard in stakeholder engagement by delivering a best-in-class experience for the community, powered by our expertise and integrated capabilities across the deucrictibant portfolio.”

Berndt Modig, Chief Executive Officer of Pharvaris, added, “Pharvaris was founded on the vision of elevating the standard of care in HAE. Today represents a landmark moment for the company and the community as a whole: deucrictibant could be the first and only oral therapy to offer injectable-like efficacy and a well-tolerated profile in on-demand treatment and prophylaxis with our two unique formulations. Pharvaris now plans to redefine disease management by uniting on-demand treatment and long-term prophylaxis within a single therapeutic franchise. This encourages us to further leverage our deep scientific expertise to bring novel therapies to those living with bradykinin-mediated diseases with unmet medical needs, beyond angioedema.”

Pharvaris plans to present additional efficacy, safety, and participant experience data from the CHAPTER-3 study at upcoming medical congresses.

The CHAPTER-4 open-label long-term extension study of deucrictibant XR for the prophylaxis of HAE attacks is ongoing.

Topline data from Part 1 of CREAATE (NCT07266805), a global, pivotal Phase 3 study evaluating orally-administered deucrictibant XR for the prevention of AAE-C1INH attacks, are anticipated in the first quarter of 2027. Enrollment in CREAATE is ongoing and progressing as planned.

Pharvaris plans to submit a New Drug Application to the U.S. Food and Drug Administration for the prophylaxis of bradykinin-mediated angioedema attacks in the first half of 2027.