Pharvaris Presents Pharmacodynamic Activity of Oral PHA121, Under Development for the Treatment of HAE, at the AAAAI Annual Meeting
- Category: Small Molecules
- Published on Saturday, 20 February 2021 11:33
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Single-dose treatment of PHA121 demonstrated effective bradykinin inhibition in healthy volunteers
ZUG, Switzerland I February 19, 2021 I Pharvaris (Nasdaq: PHVS), a clinical-stage biopharmaceutical company focused on the discovery, development, and commercialization of innovative therapies, including novel, small molecule bradykinin-B2-receptor antagonists for the treatment of hereditary angioedema (HAE) and other bradykinin-B2-receptor-mediated indications, today announced the presentation of clinical data supporting the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of PHA121 (PHA-022121) for the treatment of hereditary angioedema (HAE) at the 2021 American Academy of Allergy Asthma & Immunology (AAAAI) Virtual Annual Meeting, to be held Feb. 26 through March 1, 2021.
“The data from PHA121 continue to support our development plans to initiate studies in HAE patients this year,” said Berndt Modig, chief executive officer 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, added, “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 PK and safety observed for 72 hours. PD effects were evaluated with a nonlinear mixed-effect PK/PD model using 12 mg and 22 mg doses and compared to historical icatibant data. PK/PD 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 (AEs) 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 AEs were mild or moderate, and subsided rapidly and completely. No clinically relevant changes in safety laboratory parameters, vital signs, and ECG parameters were observed.
A copy of the poster can be viewed on the investor section of our website.
Pharvaris (Nasdaq: PHVS) is a clinical-stage biopharmaceutical company focused on bringing oral bradykinin-B2-receptor antagonists to patients. By targeting this clinically proven therapeutic target with novel small molecules, the Pharvaris team is advancing new alternatives to injected therapies for all sub-types of HAE and other bradykinin-mediated diseases. Pharvaris brings together executives with a breadth of expertise across pharmaceutical development and rare disorders, including HAE.