“Evaluating Safety Margins of the Use of Deucrictibant Extended-Release Tablet in Combination with Deucrictibant Immediate-Release Capsule” assessed human exposures across the anticipated dosing scenarios and calculated the corresponding safety margins based on available clinical and nonclinical data. The analysis demonstrated that combined use of a 40 mg deucrictibant XR tablet for prophylaxis and one or two deucrictibant IR 20 mg capsule(s) in the event of a breakthrough attack, while on prophylaxis, is supported by evidence of adequate safety margins.

A recently published post-hoc analysis of the prophylaxis CHAPTER-1 study assessed the mean duration of breakthrough attacks, in both placebo and deucrictibant arms, that were treated with a single dose of icatibant, another bradykinin B2 receptor antagonist. The comparable mean total duration of icatibant-treated attacks in the placebo-icatibant and the deucrictibant-icatibant groups provide initial evidence on the efficacy of combining use of a bradykinin B2 receptor antagonist for prophylaxis and on-demand treatment of attacks.

“These safety data, combined with the post-hoc efficacy analyses of mechanism-on-mechanism treatment of breakthrough attacks, provide evidence for the potential of the combined use of deucrictibant as a prophylactic treatment and as an on-demand medication,” said Peng Lu, M.D., Ph.D., Chief Medical Officer of Pharvaris. “Bradykinin-mediated angioedema can be prevented by administering a bradykinin B2 receptor antagonist that exceeds the therapeutic threshold to compete with bradykinin. If the plasma concentration of drug drops below this threshold, a person may be susceptible to a breakthrough attack; rapid exposure to an on-demand treatment using the same mechanism could be a compelling treatment approach in this scenario. We look forward to further exploring this strategy.”