Pharvaris announces positive top-line data from the RAPIDe-1 Phase 2 clinical study, demonstrating statistically significant results of PHVS416 as an oral on-demand treatment for HAE attacks.

RAPIDe-1 Clinical Study Design and Results
RAPIDe-1 is a Phase 2, double-blind, placebo-controlled, randomized, crossover, dose-ranging study of PHVS416 softgel capsule for the acute treatment of angioedema attacks in patients with Type I or II HAE. Seventy-four patients were enrolled across 13 countries and were randomized into one of three single dose levels of PHVS416 and placebo. The study compares symptom relief during HAE attacks and the safety of each dose of PHVS416 with placebo. In Part I of the study, participants in a non-attack state received the assigned single dose of PHVS416 at the study center to assess its pharmacokinetics and safety. In Part II, participants self-administer blinded study drug at home to treat three physician-confirmed HAE attacks with PHVS416 or placebo.

The primary endpoint of the study is the change of a three-symptom composite (skin pain, skin swelling, abdominal pain) visual analogue scale (VAS-3) score from pre-treatment to four hours post-treatment, as captured electronically using numerically assisted input. Topline data from 147 attacks collected by 62 patients show that dose levels of PHVS416 significantly reduces attack symptoms.

The statistical tests for the primary and all key secondary endpoints followed a pre-specified multiple comparison procedure to assess statistical significance for PHVS416 20 mg and 30 mg, supported by a nominal statistical analysis for PHVS416 10 mg.

PHVS416 was generally well tolerated with no treatment-related serious adverse events and no adverse events leading to treatment discontinuation. In the non-attack phase, two treatment-related adverse events were experienced by two patients; in the attack treatment phase, three treatment-related adverse events were reported for one attack treated with PHVS416 30mg (2.8%) and one treatment-related adverse event was reported for one attack treated with placebo (1.9%).

Marcus Maurer, M.D., Professor of Dermatology and Allergy at the Charité – Universitätsmedizin Berlin, and principal investigator on the RAPIDe-1 study, comments: “The expectation of people living with HAE is that next-generation HAE therapies should achieve the same or better efficacy than current standard of care while offering an improved duration of effect and better convenience. Given the study design with physician-confirmed attacks, these data showing consistent results across all endpoints are an encouraging step in that direction for PHVS416.”

Peng Lu, M.D., Ph.D., Chief Medical Officer of Pharvaris, states: “The data demonstrate rapid onset of action, symptom relief, and resolution of attacks, which support the further development of PHVS416 as a potential on-demand therapy for HAE. Further, study participants used substantially less rescue medication when taking PHVS416 to treat attacks versus when treating with placebo. The strength and durability of effect shown in the top-line data from RAPIDe-1, as well as the observed safety profile, has further enhanced our confidence in the clinical development strategy.”

Berndt Modig, CEO of Pharvaris, adds: “Seven years ago, we embarked on our journey to bring novel, oral therapies to people living with HAE based on our deep insight into the biology of HAE and an experiment, the bradykinin challenge, that guided our trial design and dose selection. The results of the RAPIDe-1 study represent another step towards a potential new, oral on-demand HAE treatment. We sincerely thank the clinical trial participants and their families, the site investigators and staff, the HAE community, and the Pharvaris team for their contributions to the RAPIDe-1 study.”

In August 2022, the U.S. Food & Drug Administration (FDA) placed clinical studies of PHA121 in the U.S., including RAPIDe-1, on hold. Pharvaris had previously announced the achievement of target enrollment across 33 sites in Canada, Europe, Israel, the UK, and the U.S. Subsequent to the clinical holds, the company continues to evaluate PHVS416 for the treatment of acute attacks for continuing participants enrolled outside the U.S.
(Source: Pharvaris)