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.
(Source: Pharvaris)
