Pharvaris presents two in-person “ePoster – Meet the Author” at the American College of Allergy, Asthma & Immunology (ACAAI) Annual Scientific Meeting 2022.
“The data demonstrate the optimized pharmacokinetic and tolerability profiles of Pharvaris’ drug candidates that are in clinical development for the treatment of HAE,” says Peng Lu, M.D., Ph.D., Chief Medical Officer of Pharvaris. “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.”
Development of PHVS719: an Oral Extended-Release Bradykinin B2 Receptor Antagonist to Prevent Hereditary Angioedema Attacks
Pharmacokinetic properties of PHA121 were evaluated to support the intended therapeutic use of PHVS719 for the prophylactic treatment of HAE attacks using preclinical and clinical experimental models. Colonic absorption of PHA121 was investigated as a requisite for prolonged absorption of the extended-release formulation under development. In rodents, plasma concentrations following oral and intracolonic administrations of PHA121 were comparable, providing evidence that PHA121 can be systemically absorbed by colonic mucosa. In humans, high oral bioavailability and low fecal excretion further indicate almost-complete absorption in the gastrointestinal tract. Together, these data support clinical development of the extended-release tablet PHVS719 as a once-daily prophylactic treatment of HAE attacks.
Pharmacokinetics of PHVS719, extended-release tablet formulation of PHA121, a first-in-class oral human bradykinin B2-receptor antagonist
In the Phase 1 pharmacokinetic study of PHVS719, 10 healthy subjects received, in a randomized order, two different doses of PHVS719 extended-release tablets (XR1 at 20 mg and XR2 at 40 mg), in fasting and in fed conditions, and one dose of PHVS416 20 mg in fasting conditions. Measurement of time-to-reach-therapeutic-exposure-levels for PHA121 above the EC85 of 13.8 ng/mL showed that after administration of XR1 and XR2, therapeutic plasma concentrations were achieved within approximately two hours. Concentrations of PHA121 remained at therapeutic levels for at least 30 hours with XR2. Food intake did not have significant effects on the time to reach therapeutic exposure of PHA121 nor on the time at which concentrations remained at therapeutic levels. The 24-hour area-under-the-curve exposure of PHA121 after XR2 was comparable to that observed in Phase 1 studies with PHVS416 softgel capsules dosed at 20 mg bid with food. Administration of both PHVS719 and of PHVS416 were well tolerated. No severe nor serious treatment-emergent adverse events were reported, with no specific safety pattern or trend in number or type of events. The 10 treatment-emergent adverse events that were reported in 50% of the participating subjects were mainly of Grade 1 severity or of Grade 2 severity, occurred after only one of the administrations of study drugs, and all completely resolved. Two of these events, namely neck pain and post-procedural hypotension, were considered as not related to the study drug. PHVS416, a softgel capsule formulation of PHA121 is being evaluated for safety and efficacy outcomes in CHAPTER-1, a Phase 2 proof of concept clinical trial, which is currently ongoing in countries outside the U.S. The U.S. Food and Drug Administration has placed on hold on clinical trials of PHA121 in the U.S.
(Source: Pharvaris)
