PHVS416, an investigational soft capsule formulation containing the oral antagonist of bradykinin B2 receptor PHA121, has demonstrated a rapid onset of action, symptom relief, and resolution of hereditary angioedema (HAE) attacks, according to results of the RAPIDe-1 trial presented at the 2023 HAE International (HAEi) Regional Conference APAC.
The study authors announced that the RAPIDe-1 trial met its primary endpoint—the change in visual analog score (VAS)-3 from pretreatment to 4 hours post-treatment—as well as all key secondary endpoints.
“Currently approved on-demand therapies for HAE attacks are administered intravenously or subcutaneously with substantial treatment burden due to the time required for preparation and administration as well as potential occurrence of pain, discomfort, or other injection site reactions, leading to treatment of many attacks being delayed or forgone,” the study authors noted.
“Unmet need exists for on-demand oral therapies that are effective and well-tolerated and may reduce the treatment burden enabling prompt administration as recommended by clinical guidelines.”
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This seems to be the case for PHVS416, which is not yet approved by regulatory authorities. The investigational treatment reduced the use of rescue medications and was well tolerated at all dose levels, according the results. There were no treatment-related serious adverse events, adverse events of severe severity, or adverse events leading to treatment discontinuation.
RAPIDe-1 is a placebo-controlled, double-blind, 3-dose level study designed to evaluate the efficacy of orally administered PHA-121 for the acute treatment of attacks in patients with HAE.
The study, which enrolled 74 patients from 13 sites in Canada, Europe, Israel, the United Kingdom, and the United States, comprised 2 parts. In part 1, study participants were randomized to receive 1 of 3 doses of PHVS416 (10, 20, or 30 mg) and given the initial dose at the study site for pharmacokinetic and safety assessment. In part 2, all participants were treated for up to 3 attacks, with 2 attacks being treated with PHVS416 and 1 with placebo.
In August 2022, the US Food and Drug Administration (FDA) placed a hold on the clinical trials of PHA121 in the United States based on its review of nonclinical data. Nonetheless, the agency agreed to partially lift the clinical hold on the RAPIDe-1 trial.
Riedl MA, Anderson J, Aygören-Pürsün E, et al. Efficacy and safety of bradykinin B2 receptor antagonism with oral PHVS416 in treating hereditary angioedema attacks: results of RAPIDe-1 phase 2 trial. Presentation presented at: 2023 HAE International (HAEi) Regional Conference APAC; March 17-19, 2023; Bangkok, Thailand.