Pharvaris Inc. presented phase 1 data supporting the safety of PHVS719 in the prophylactic treatment of hereditary angioedema (HAE) attacks at the recent American College of Allergy, Asthma & Immunology annual meeting.
PHVS719 is an extended-release tablet formulation of PHA121, a first-in-class oral human bradykinin B2 receptor antagonist that is more potent than icatibant (Firazyr®) at competing and inhibiting bradykinin.
“Upon administration of a single dose of PHVS719 extended-release XR2 [extended release] tablet, therapeutic exposure was reached within few hours and was sustained for >24 hours, independently from food intake,” the authors concluded in their poster. Therapeutic plasma concentrations were achieved within approximately 2 hours and were maintained for at least 30 hours.
The open-label, single-dose, randomized, 5-period, 5-sequence, crossover, explorative phase 1 study evaluated the bioavailability of PHVS719 (20 or 40 mg, under fasting or fed conditions) in comparison with a single dose of PHVS416 soft capsule, a PHA121 formulation for oral on-demand treatment of HAE attacks, under fasting conditions.
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The 24-hour area-under-the-curve exposure of PHA121 after a single dose of PHVS719 (40 mg) was comparable with that observed in phase 1 studies with PHVS416 soft capsules dosed at 20 mg twice a day with food.
Moreover, both PHVS719 and PHVS416 were well-tolerated. Of the 10 healthy adult male volunteers, 8 completed the study. One of the participants discontinued the study due to a treatment-emergent adverse event (TEAE) of neck pain. Five patients reported a total of 10 TEAEs that were mainly of grade 1 or 2 severity. Two were assessed as unrelated to the study drug (neck pain and postprocedural hypotension). TEAEs occurred after only 1 of the administrations of the study drugs, and all completely resolved.
The US Food and Drug Administration has placed a clinical hold on 2 clinical trials of PHA121.
Groen K, Crabbé R, Knolle J, Gibson C, Lesage A, Lu P. Pharmacokinetics of PHVS719, extended-release tablet formulation of PHA121, a first-in-class oral human bradykinin B2-receptor antagonist. Poster presented at: American College of Allergy, Asthma & Immunology Annual Scientific Meeting 2022; November 10-14, 2022; Anaheim, CA.