Shares of Pharvaris (NASDAQ: PHVS) climbed 17.3% to $41.36 in early trading Tuesday after the company announced that its once-daily oral drug, deucrictibant XR, significantly reduced attacks in patients with hereditary angioedema (HAE) in a pivotal Phase 3 trial. The stock had surged as much as 27.7% to $45 in premarket trading before pulling back.
CHAPTER-3 Trial Results
The CHAPTER-3 study, a 24-week, double-blind, placebo-controlled trial involving 85 adolescents and adults across 21 countries, met its primary endpoint with an 83% reduction in monthly attack rate (95% CI: 72%–90%, p<0.0001). Patients receiving the 40-milligram extended-release tablet experienced an average of only 0.35 attacks per month, compared with 2.06 for placebo. In the subgroup of 80 patients with Type 1 or Type 2 HAE, the reduction was even higher at 87%, though this analysis was not adjusted for multiplicity.
All secondary efficacy endpoints were also met with statistical significance, and the protective effect appeared within the first week and was sustained throughout the 24-week treatment period. The company plans to present additional efficacy, safety, and patient-experience data at future medical conferences.
Safety Profile
The initial safety data were favorable, with most treatment-emergent adverse events rated mild or moderate. There were no treatment-related serious adverse events, and only one patient in each arm discontinued due to an adverse event. This clean safety signal is crucial for a preventive therapy that patients may take long-term.
Strategic Implications
The positive outcome de-risks Pharvaris's broader development strategy, which aims to leverage the same active molecule for both prevention (extended-release tablet) and acute treatment (immediate-release capsule). The immediate-release formulation is already under FDA review with a target action date of April 23, 2027, while the company plans to submit the U.S. application for the preventive formulation in the first half of 2027.
However, Pharvaris will enter a competitive market. BioCryst's Orladeyo is already approved as a once-daily oral preventive, and KalVista's Ekterly became the first oral acute treatment in July 2025. Injectable preventives are also well established. The 0.35 monthly attack rate provides a strong efficacy argument, but cross-trial comparisons with approved drugs are unreliable due to differences in trial design and patient populations.
Financial Position
As of June 30, Pharvaris held €318 million in cash and cash equivalents, with a second-quarter net loss of €47.8 million. The balance sheet is sufficient to support ongoing development and regulatory filings, but commercial launch costs for two potential products could increase spending before any revenue is generated.
The stock's retreat from its premarket high reflects the remaining uncertainties: regulatory review, long-term durability, the complete safety dataset, and the company's ability to capture market share in a well-established rare-disease space. While CHAPTER-3 answered the most critical clinical question favorably, the path to commercial success remains to be seen.
