At the 2021 American Academy of Allergy Asthma & Immunology (AAAAI) Virtual Annual Meeting Pharvaris presents clinical data supporting the pharmacokinetic and pharmacodynamic profiles of PHA121 (PHA-022121) for the treatment of HAE.
“The data continue to support our development plans to initiate studies in HAE patients this year,” says Berndt Modig, CEO and co-founder of Pharvaris. “There remains an unmet medical need for highly effective oral therapies with favorable safety profiles. We will continue to evaluate PHA121 for both on-demand and prophylactic treatment of HAE through our soft-capsule formulation, PHVS416, and tablet formulation, PHVS719.”
Peng Lu, M.D., Ph.D., chief medical officer of Pharvaris, adds: “Orally dosed PHA121 was rapidly absorbed and exceeded projected efficacious therapeutic thresholds within 15 minutes with or without food. Using bradykinin-challenge-induced surrogate markers, pharmacodynamic results suggest that PHA121 may provide longer pharmacological effect with a single oral dose than icatibant. We look forward to exploring the therapeutic potential of this compound in multiple clinical studies this year.”
PHA121 was orally administered in two double-blind, placebo-controlled single-ascending-dose studies up to 50 mg, with pharmacokinetic and safety observed for 72 hours. Pharmacodynamic effects were evaluated with a nonlinear mixed-effect pharmacokinetic/pharmacodynamic model using 12 mg and 22 mg doses and compared to historical icatibant data. Pharmacokinetic/pharmacodynamic analysis showed significant inhibition of bradykinin-induced hemodynamic changes with an average composite EC50 of 2.4 ng/mL and EC85 of 13.8 ng/mL. Quantitative modeling indicates that single oral doses of PHA121 will maintain pharmacologically active drug levels for a substantially longer time than 30 mg of subcutaneous icatibant.
Adverse events were reported by 25% of the subjects in the combined group of all subjects treated with PHA121, identical to the 25% incidence with placebo. All adverse events were mild or moderate, and subsided rapidly and completely. No clinically relevant changes in safety laboratory parameters, vital signs, and ECG parameters were observed.