Pharvaris has reported positive topline results from the phase 3 CHAPTER-3 study of deucrictibant extended-release (XR) tablet, showing an 83% reduction in mean monthly hereditary angioedema (HAE) attack rate versus placebo (P <.0001) across all 3 HAE types in adolescents and adults.¹
The study is the first and only prophylaxis phase 3 program to evaluate all 3 HAE types, including HAE with normal C1 inhibitor, a population without a dedicated oral prophylactic option in this analysis.¹ Data from CHAPTER-3 will support marketing authorization applications, which Pharvaris plans to begin submitting in the first half of 2027.¹
"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," said lead investigator Marc A. Riedl, MD, MS, professor of medicine and clinical director of the US Hereditary Angioedema Association (HAEA) Angioedema Center at the University of California San Diego, in a statement.
Deucrictibant XR CHAPTER-3 Trial Design and Primary Results
CHAPTER-3 is a global, double-blind, placebo-controlled phase 3 study evaluating deucrictibant XR 40 mg once daily for prevention of HAE attacks in adolescents and adults.² The trial 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.²
Deucrictibant XR reduced the mean monthly attack rate by 83% compared with placebo across all HAE types (P <.0001).² In the subgroup of 80 participants with HAE type 1 or type 2, the reduction reached 87% versus placebo.² Primary endpoint results were consistent across subgroups, and protection was evident within the first week of treatment and sustained through 24 weeks.²
Deucrictibant XR Secondary Endpoints and Safety Profile
Key Takeaways
- CHAPTER-3 met its primary endpoint, showing an 83% reduction in mean monthly HAE attack rate versus placebo across all 3 HAE types (P <.0001), and 87% in HAE Type 1/2
- All secondary efficacy endpoints were met with statistical significance, with protection evident within the first week and sustained through 24 weeks
- Pharvaris plans to submit marketing authorization applications for deucrictibant XR starting in the first half of 2027, alongside an ongoing FDA review of deucrictibant IR for on-demand treatment
All secondary efficacy endpoints, assessed sequentially under a multiplicity-control procedure, were met with statistical significance.¹ Pharvaris reported robust reductions in attack rate from baseline alongside increases in the percentage of participants who were attack-free during the study.¹
Deucrictibant XR was well tolerated in CHAPTER-3, with most treatment emergent adverse events mild or moderate in severity.¹ No treatment-related serious adverse events were reported.¹ One participant in each treatment group discontinued due to an adverse event.¹
The CHAPTER-4 open-label long-term extension study of deucrictibant XR is ongoing to characterize the durability of effect and safety beyond the primary study period.¹ Pharvaris did not report a specific timepoint for CHAPTER-4 topline data in this release.¹
Pharvaris also has an NDA under FDA review for deucrictibant immediate-release capsule for on-demand treatment of HAE attacks and plans to submit a separate NDA for deucrictibant XR for prophylaxis in the first half of 2027.¹ The company is separately evaluating deucrictibant XR in the phase 3 CREAATE study for acquired angioedema due to C1 inhibitor deficiency, with topline data from part 1 anticipated in the first quarter of 2027.¹
"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," said Pharvaris President Peng Lu, MD, PhD, in a statement. "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."¹
References
A study to evaluate deucrictibant extended-release tablet for the prophylaxis of hereditary angioedema attacks (CHAPTER-3). ClinicalTrials.gov. https://clinicaltrials.gov/study/NCT06669754
