Pharvaris Inc. revealed pharmacokinetic data for PHA121, a bradykinin B2 receptor antagonist, supporting clinical development of an extended-release formulation, PHVS719, as a once-daily prophylactic treatment of hereditary angioedema (HAE) attacks.

The results were presented at the recent American College of Allergy, Asthma & Immunology annual meeting.

“The data presented at ACAAI demonstrate the optimized pharmacokinetic and tolerability profiles of Pharvaris’ drug candidates that are in clinical development for the treatment of HAE,” said Peng Lu, MD, PhD, chief medical officer of Pharvaris in a news release. “PHVS719 is designed to be a once-daily prophylactic treatment for the prevention of HAE attacks, as supported by data demonstrating compound absorption in the colon and maintained exposure above predicted therapeutic levels. The cross-over pharmacokinetic data described in the second poster support the dosing regimen in CHAPTER-1, a phase 2 study evaluating PHVS416 as a proof of concept of PHVS719 for the prophylactic treatment of HAE.”


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The researchers investigated the colonic absorption of PHA121 as a requisite for prolonged absorption of the extended-release formulation under development. Rats receiving a single 2 mg/kg dose of PHA121 orally or via intracolonic administration had comparable PHA121 plasma concentrations. Moreover, the high oral bioavailability (57%) and low fecal excretion (3.2%) of PHA121 in humans further suggested an almost complete absorption in the gastrointestinal tract.

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To assess the dissolution of the extended-release formulation, PHVS719, the researchers performed an in vitro dissolution experiment. The results showed a linear dissolution over time under fed and fasted conditions.

The safety and efficacy of PHA121 for the prevention of HAE attacks are being evaluated in the phase 2 CHAPTER-1 proof-of-concept clinical trial. However, the US Food and Drug Administration has placed a clinical hold on the clinical trials of PHA121 based on its review of nonclinical data.

Reference

Lesage A, Gibson C, Knolle J, Groen K, Crabbé R, Lu P. Development of PHVS719: an oral extended-release bradykinin B2 receptor antagonist to prevent hereditary angioedema attacks. Poster presented at: American College of Allergy, Asthma & Immunology Annual Scientific Meeting 2022; November 10-14, 2022; Anaheim, CA.

Pharvaris to present PHVS416 and PHVS719 clinical data for treatment of HAE at the ACAAI annual scientific meeting 2022. News release. Pharvaris NV; November 10, 2022.