Pharvaris Presents Pharmacokinetic and Pharmacodynamic Data for Oral PHA121, Under Development for the Treatment of HAE, at 12th C1 Inhibitor Deficiency and Angioedema Workshop
- Category: Small Molecules
- Published on Friday, 04 June 2021 15:35
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ZUG, Switzerland I June 04, 2021 I Pharvaris (Nasdaq: PHVS), a clinical-stage company focused on the development and commercialization of novel oral bradykinin-B2-receptor antagonists for the treatment of hereditary angioedema (HAE) and other bradykinin-B2-receptor-mediated indications, today announced that Anne Lesage, Ph.D., chief early development officer at Pharvaris, will present bradykinin challenge data supporting the pharmacokinetic (PK) and pharmacodynamic (PD) profile of PHA121 (PHA-022121) for the treatment of hereditary angioedema (HAE), at the 12th C1 Inhibitor Deficiency and Angioedema Workshop, to be held virtually June 3-6, 2021.
“Pharvaris is proud to be a sponsor for the 12th C1 Inhibitor Deficiency and Angioedema Workshop,” said Dr. Lesage. “Findings presented here from pre-clinical and clinical studies, particularly from in vivo bradykinin challenge studies, show that PHA121 demonstrates faster onset than icatibant in head-to-head preclinical studies and, compared to published data, is consistently more potent showing longer duration bradykinin-BR2-antagonist activity than icatibant in human pharmacodynamic studies. These data position PHA121 as a potentially valuable treatment option for both on-demand and prophylactic treatment of HAE.”
Berndt Modig, chief executive officer and co-founder of Pharvaris added, “Our data demonstrate a favorable pharmacokinetic and pharmacodynamic profile of PHA121 – providing strong proof of mechanism for PHA121 and a foundation for the dose regimens to be further evaluated for HAE as Pharvaris continues progressing our clinical programs using our PHVS416 and PHVS719 product formulations.”
Pharvaris established a proof-of-concept model for HAE in non-human primates using bradykinin, an endogenous peptide known to mediate signs and symptoms of HAE. The model was validated utilizing icatibant, a marketed injectable B2 receptor antagonist, providing back-translation from human clinical experience with icatibant. The objective of the study was to investigate the ability of PHA121 to attenuate blood-pressure changes induced by bradykinin injection. In this model, PHA121 inhibited bradykinin-induced changes in blood pressure at all doses tested (0.1, 0.3, 1, 3, and 10 mg/kg given orally) with a faster onset of action than icatibant and the duration of the effect was dose dependent.
PHA121 was also orally administered in two double-blind, placebo-controlled single-ascending-dose studies up to 50 mg, with pharmacokinetics (PK) and safety observed for 72 hours, in healthy volunteers. Pharmacodynamic (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. Single-dose treatment of PHA121 demonstrated effective bradykinin inhibition. 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.
A copy of the oral presentation can be viewed on the investor section of our website.
PHVS416 is a softgel capsule formulation containing PHA121, a highly potent, specific, and orally bioavailable competitive antagonist of the bradykinin B2 receptor. Pharvaris is developing this formulation to provide rapid exposure of attack-mitigating medicine in a convenient, small oral dosage form. PHVS416 is currently in Phase 2 clinical development for the on-demand treatment of HAE.
PHVS719 is an extended-release tablet formulation containing PHA121, a highly potent, specific, and orally bioavailable competitive antagonist of the bradykinin B2 receptor. Pharvaris is developing this formulation to provide sustained exposure of attack-preventing medicine in a convenient, small oral dosage form. PHVS719 is currently in preclinical development for the prophylactic treatment of HAE.
PHA121 (PHA-022121) is a highly potent, specific, and orally bioavailable competitive antagonist of the bradykinin B2 receptor that has completed Phase 1 clinical development for the treatment of HAE. PHA121 utilizes the same mechanism as icatibant, the leading therapy for on-demand treatment of HAE. Pharvaris is developing this novel small molecule for on-demand and prophylactic treatment of HAE and other bradykinin-mediated diseases through formulations optimized for each setting. Data from single- and multiple-ascending-dose Phase 1 studies in healthy volunteers demonstrate rapid exposure and predictable linear pharmacokinetics at doses up to 50 mg. In a bradykinin-challenge study in healthy volunteers, PHA121 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, approximately four-fold more potent than historical data for icatibant. 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. PHA121 has been observed to be well-tolerated at all doses studied to date.
Pharvaris is a clinical-stage 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. The Company brings together executives with a breadth of expertise across pharmaceutical development and rare disorders, including HAE. For more information, visit https://pharvaris.com/.