Pharvaris N.V. (Nasdaq: PHVS) has reported an 83% reduction in monthly hereditary angioedema (HAE) attack rate with deucrictibant extended-release (XR) tablet versus placebo in the pivotal CHAPTER-3 Phase III study, clearing the path for a prophylaxis NDA submission planned for H1 2027. Deucrictibant has the potential to become the first oral HAE therapy spanning both on-demand treatment and long-term prophylaxis, with this week's positive readout for the XR formulation following an approval filing for the immediate-release (IR) formulation made in July 2026.
The global, double-blind, placebo-controlled trial randomized 85 adolescents and adults with all three HAE types — including HAE with normal C1 inhibitor, a subtype excluded from most approved agents' labels — across 21 countries in a 2:1 ratio to deucrictibant XR 40 mg once daily or placebo for 24 weeks. The 83% attack rate reduction (p<0.0001) was consistent across subgroups. Among the 80 of these participants with HAE Type 1 or Type 2, the reduction was 87%. All secondary efficacy endpoints were met sequentially under a multiplicity-control procedure, and protection was evident within the first week and sustained through the full treatment period. Most treatment-emergent adverse events were mild or moderate, no treatment-related serious adverse events were reported, and one participant in each arm discontinued due to an adverse event.
Deucrictibant blocks the bradykinin B2 receptor, the downstream effector of vascular permeability that drives swelling attacks regardless of which upstream pathway generates bradykinin — a mechanistic property that makes it potentially relevant across HAE subtypes and in acquired angioedema due to C1 inhibitor deficiency (AAE-C1INH), an indication for which no approved prophylactic currently exists.
The HAE prophylaxis market has become increasingly competitive. BioCryst’s Orladeyo (berotralstat), a once-daily oral plasma kallikrein inhibitor, has been approved in the US since 2020, while CSL Behring’s once-monthly injectable Factor XIIa inhibitor Andembry and Ionis Pharmaceuticals’ prekallikrein-targeting Dawnzera expanded the market in 2025. Deucrictibant XR would add a second oral mechanism, differentiating itself by blocking the bradykinin B2 receptor downstream of kallikrein.