From its Phase 1 multiple-ascending-dose study demonstrating PHA121’s pharmacokinetics and tolerability Pharvaris announces that PHA121 was well tolerated at all doses studied, with approximately dose-proportional exposure.
“We are encouraged by these results to continue development of PHA121 as an oral treatment for HAE,” says Berndt Modig, CEO and co-founder of Pharvaris. “In 2021, we will explore the therapeutic potential of PHA121 for both acute and prophylactic treatment of HAE. Our upcoming Phase 2 studies will utilize PHVS416, a soft capsule formulation containing PHA121.”
The Phase 1 randomized, double-blind, placebo-controlled, multiple ascending dose trial examined the safety, tolerability, and pharmacokinetics of PHA121 in healthy volunteers. The trial included 38 healthy subjects dosed twice daily (BID) for 10 days in four sequential dosing cohorts, ranging from 12 to 50 mg. During the study, PHA121 was well tolerated up to the highest dose of 50 mg BID. All reported treatment-emergent adverse events (TEAEs) were mild in intensity and resolved completely. The total incidence and type of TEAEs were similar between active drug and placebo groups. Lab safety, vital signs, and ECG parameters remained well within normal limits in all subjects. The pharmacokinetic profile suggests that therapeutic drug levels of PHA121 were achieved in day 1 and steady-state plasma concentrations were reached within 72 hours.
PHVS416 is a soft capsule formulation containing PHA121 (PHA-022121), a highly potent, specific, and orally bioavailable competitive antagonist of the bradykinin B2 receptor. Pharvaris is developing this formulation to provide rapid exposure of attack-mitigating medicine in a convenient, small oral dosage form.
PHA121 (PHA-022121) is a highly potent, specific, and orally bioavailable competitive antagonist of the human bradykinin B2 receptor currently in Phase 1 clinical development for the treatment of HAE. PHA121 utilizes the same mechanism as icatibant, the leading therapy for on-demand treatment of HAE. Pharvaris is developing this novel small molecule for on-demand and prophylactic treatment of HAE and other bradykinin-mediated disease through formulations optimized for each setting.