Pharvaris N.V. 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 (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. 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.

Throughout 12 weeks of treatment in CHAPTER-1, both doses of deucrictibant were well-tolerated. There were no serious adverse events, no severe treatment-emergent adverse events, and no adverse events leading to treatment discontinuation. In August 2022, the U.S. Food & Drug Administration (FDA) placed clinical studies of deucrictibant, including CHAPTER-1, on hold.

Pharvaris notified country-specific regulatory authorities in Canada, Europe, Israel, and the UK regarding the clinical holds in the U.S., and the regulatory status of deucrictibant outside the U.S. has not been affected. In June 2023, Pharvaris announced the removal of the clinical hold of deucrictibant for the on-demand treatment of HAE in the U.S.Pharvaris has completed the 26-week rodent toxicology study requested by the FDA, which it believe met its objective. Pharvaris is preparing to submit the study results to the FDA by the end of the year.

However, neither the nature nor timing of the response from FDA is certain.