At the EAACI Hydrid Congress 2021, Pharvaris presented clinical data supporting the multiple-dose safety and pharmacokinetic (PK) profile of PHA121 (PHA-022121) for the treatment of HAE.
The double-blind, randomized, placebo-controlled, multiple ascending dose study included 38 male and female healthy volunteers. PHA121 was orally administered after standardized meals twice daily (BID) for 10 days in four sequential dosing cohorts, ranging from 12 to 50 mg, with safety and PK assessments during treatment and follow-up for 72 hours after the last dose. PHA121 was well-tolerated up to the highest dose of 50 mg BID. All reported treatment-emergent adverse events (TEAEs) were mild in intensity and resolved completely. The total incidence and type of AEs was comparable between active and placebo groups.
The data also show that PHA121 was well absorbed with median times to reach peak plasma levels within 1.00 to 1.75 hours after dosing with standard meals. On both Day 1 and Day 10, plasma exposure of PHA121 increased approximately dose-proportionally over the dose range from 12 to 50 mg with a mean half-life ranging from 4.8 to 7.3 hours after Day 10. At steady state, which was generally reached within three days of treatment, plasma levels of PHA121 remained consistently above the therapeutic threshold EC85 for all doses (as determined in a human bradykinin challenge previously described).
“The pharmacokinetic profile demonstrated in this study suggests that the therapeutic effect of PHA121 can be achieved as early as the first day of dosing, with steady-state plasma levels achieved within three days. PHA121 was well-tolerated in healthy volunteers up to 50 mg dosed twice a day for 10 days,” says Peng Lu, M.D., Ph.D., Chief Medical Officer of Pharvaris. “Coupled with our bradykinin challenge data, which has shown potent inhibition of bradykinin-induced hemodynamic effects, the PK and safety data observed in this study supports future development to assess the efficacy and safety of prophylactic use of PHA121 in HAE patients.”
Berndt Modig, CEO and co-founder of Pharvaris adds: “Bradykinin-B2-receptor antagonism has been demonstrated to be effective in treating acute HAE attacks but is currently not available as oral treatment. Pharvaris remains committed to providing patients with oral alternatives both for on-demand and prophylactic treatment in HAE via our softgel capsule formulation, PHVS416, and extended-release tablet formulation, PHVS719.”
A copy of the e-poster, titled “Multiple dose administration of PHA-022121, an orally available, bradykinin B2 receptor antagonist is well tolerated and shows a favorable pharmacokinetic profile for prophylactic treatment of HAE,” can be viewed on the Investor section of the company’s website at https://ir.pharvaris.com/news-events/events-presentations.