Clinical data support the development of bradykinin B2 receptor antagonists for on-demand and prophylactic treatment of hereditary angioedema (HAE), according to a news release by Pharvaris, the company developing two such drugs.
The data were presented at the Bradykinin Symposium 2022 in Berlin, Germany.
“Inhibition of bradykinin signaling via B2 receptor antagonism addresses the fundamental mechanism that leads to [hereditary angioedema] symptoms,” Anne Lesage, PhD, chief early development officer at Pharvaris, said.
The company said that PHA121, the active ingredient in the experimental treatments, was 25 times more potent than icatibant as an inhibitor of bradykinin interaction with endogenous human B2 receptors. Studies have demonstrated that tailored formulations of PHA121 are likely to be effective in treating hereditary angioedema attacks, as well as reducing their likelihood of occurring.
Read more about hereditary angioedema epidemiology
In healthy volunteers undergoing a bradykinin challenge study, PHA121 was able to significantly inhibit hemodynamic changes induced by bradykinin with an average composite half maximal effective concentration (EC50) of 2.4 ng/mL, demonstrating potency that was around 4-fold greater than that of icatibant. PHA121 was also well tolerated at all doses studied, according to Pharvaris.
PHA121 is the active ingredient in both PHVS416 and PHVS719, two orally bioavailable competitive antagonists of the bradykinin B2 receptor. Studies demonstrate that a single dose of PHVS416 in healthy volunteers exceeded predicted therapeutically efficacious levels in under 15 minutes. As for PHVS719, extended-release profiling supports once-daily dosing as a prophylactic treatment of hereditary angioedema.
“The pharmacokinetic data shown for the two oral formulations of PHA121 continue to support the investigation of PHVS416 and PHVS719 for the treatment of [hereditary angioedema],” Dr. Lesage said.
Pharvaris highlights data supporting clinical development program for hereditary angioedema at the 2022 Bradykinin Symposium. News release. Pharvaris; September 16, 2022.