A Pharvaris drug led to speedy relief and symptom resolution from the sudden swelling attacks caused by a rare genetic disorder, preliminary Phase 3 clinical trial results that pave the way for an FDA submission the company plans to file next year. If approved, the Pharvaris capsule could become just the second oral option for patients needing an acute treatment for the attacks caused by this disease, hereditary angioedema (HAE).
Pharvaris is developing two formulations of its drug, deucrictibant. The results reported Wednesday are for the immediate-release capsule as an on-demand treatment for HAE attacks. A separate ongoing Phase 3 test is evaluating an extended-release version of the drug for prophylactic HAE treatment.
HAE is an inherited disease caused by deficiency or dysfunction of C1 esterase, a protein that regulates other proteins involved in swelling and inflammation. Patients who have this disease can develop sudden and painful swelling attacks throughout the body. Attacks that affect the airway can become fatal. The drugs available for treating acute HAE attacks include injectable C1 esterase inhibitors marketed by Pharming Group and CSL Behring.
Deucrictibant is an oral small molecule inhibitor of the bradykinin B2 receptor, an approach intended to prevent HAE attacks that stem from signaling through this receptor. The results reported Wednesday are from a placebo-controlled Phase 3 test of the drug as an on-demand treatment in 134 HAE patients age 12 and older. The main goal was measuring the time to symptom relief according to a seven-point scale used to evaluate the change in HAE attack symptoms.
According to the data readout, the median time to onset of symptom relief was 1.28 hours. This measure was not estimable for the placebo arm. The study drug also met secondary goals with end of the progression of attack symptoms achieved in a median 17.47 minutes compared to 228.67 minutes for the placebo group. Complete symptom resolution for the Pharvaris drug was a median of 11.95 hours. Deucrictibant, a single tablet taken at the first sign of an HAE attack, was well tolerated. No discontinuations were reported due to treatment emergent adverse events; no safety signals were identified.
Patients gained the option of an oral treatment for acute HAE attacks over the summer with FDA approval of Ekterly from KalVista Pharmaceuticals. Taken as two tablets at the sign of an HAE attack, Ekterly is an oral small molecule inhibitor of kallikrein, a different protein involved in HAE swelling.
In a note sent to investors, Leerink Partners analyst Joseph Schwartz said the firm views the deucrictibant data as very strong. Cross-trial comparisons are always tricky, but the speed of symptom relief for Pharvaris’s pill is incrementally faster than Ekterly, which showed symptom relief in a median 1.61 hours for the 300 mg dose and a median 1.79 hours for the 600 mg dose. But Schwartz noted stronger differentiation for deucrictibant on the measure of time to complete symptom relief: a median 11.95 hours for the Pharvaris drug compared to more than 24 hours for Ekterly. Schwartz said the strength of Ekterly’s launch validates the opportunity for the Pharvaris drug.
“Overall, we continue to believe that the market is large enough for multiple players, especially as it continues to expand with the approval of new options,” he said.
Pharvaris said it expects to submit an FDA new drug application for deucrictibant in the first half of 2026. Preliminary results from the Phase 3 test of the extended-release version of the drug are expected in the second half of next year. Yet another Phase 3 study is ongoing testing the drug in acquired angioedema due to C1 inhibitor deficiency.
Photo by Flickr user Jernej Furman via a Creative Commons license
