- Primary endpoint met; 40 mg/day orally administered deucrictibant significantly reduced mean monthly attack rate by 84.5% (p=0.0008) compared to placebo
- 92.3% reduction in occurrence of moderate and severe attacks
- 92.6% fewer attacks treated with on-demand medication by participants
- Deucrictibant well-tolerated
- Pharvaris to host a conference call today at 8:00 a.m. EST
ZUG, Switzerland, Dec. 06, 2023 (GLOBE NEWSWIRE) -- Pharvaris (NASDAQ:PHVS), a clinical-stage company developing novel, oral bradykinin B2 receptor antagonists to treat and prevent hereditary angioedema (HAE) attacks, today announced positive top-line data from the CHAPTER-1 Phase 2 clinical study meeting its primary endpoint, with deucrictibant demonstrating statistically significant and clinically meaningful results of deucrictibant as an oral preventative treatment for people living with HAE. Pharvaris plans to present data from the study at future medical meetings.
CHAPTER-1 Clinical Study Design and Results
CHAPTER-1 (NCT05047185) is a double-blind, placebo-controlled Phase 2 study evaluating the efficacy as well as the safety and tolerability of deucrictibant for long-term prophylaxis against angioedema attacks in HAE-1/2. In the study, 34 participants were enrolled globally and randomized to receive one of two doses of deucrictibant (20 mg/day or 40 mg/day) or placebo for 12 weeks of treatment. Deucrictibant immediate-release capsule (PHVS416) was dosed twice-a-day as a proof-of-concept for the once-daily deucrictibant extended-release tablet (PHVS719), which is the intended formulation for the prophylactic treatment of HAE. The open-label portion of the CHAPTER-1 study is ongoing at the 40 mg/day dose.
The study's primary endpoint measured the time-normalized number of investigator-confirmed HAE attacks during the treatment period. The monthly attack rate was reduced by 84.5% (p=0.0008) compared to placebo in participants who received 40 mg/day of deucrictibant.
Marc A. Riedl, M.D., M.S., Professor of Medicine, Clinical Director of the US Hereditary Angioedema Association (HAEA) Angioedema Center at the University of California San Diego (UCSD), Clinical Service Chief for Allergy/Immunology at UCSD, and principal investigator in the CHAPTER-1 study, commented, "The HAE community is seeking highly effective, well-tolerated, and less burdensome therapies. The CHAPTER-1 data represent an important step forward in the evolution of HAE treatment. Given these encouraging results, deucrictibant has the potential to significantly improve clinical outcomes for people living with HAE."
Peng Lu, M.D., Ph.D., Chief Medical Officer of Pharvaris, stated, "Deucrictibant is the first HAE treatment with the potential to combine injectable-like efficacy and a favorable safety profile with the convenience of an oral therapy. The study demonstrates, for the first time ever, that antagonism of the bradykinin B2 receptor can provide early and sustained protection from HAE attacks, including substantial reduction of moderate and severe attacks, with clinically meaningful improvement in health-related quality of life. We look forward to advancing the development of deucrictibant for the prevention of HAE attacks."
Berndt Modig, Chief Executive Office of Pharvaris, added, "We sincerely thank the clinical trial participants and their caregivers, the site investigators and staff, the HAE community, and the Pharvaris team for their contributions to the CHAPTER-1 study. These study results, together with the compelling data from our on-demand program, further strengthens our confidence that deucrictibant can become the preferred option to treat as well as prevent HAE attacks."
In the analysis of the secondary endpoints, deucrictibant demonstrated clinically meaningful improvement in the severity of attacks and a decrease in the number of attacks treated with on-demand medication. Participants on deucrictibant treatment experienced a meaningful improvement in their quality of life. The table below lists additional study findings:
Placebo N=11 | 20 mg/day N=11 | 40 mg/day N=12 | |
Monthly attack rate – LS Mean (95% CI)* | |||
Moderate or severe attacks | 1.50 (0.91, 2.50) | 0.26 ... |