CSL presents results from the pivotal placebo-controlled Phase 3 VANGUARD clinical trial of garadacimab (CSL312), CSL’s investigational first-in-class monoclonal antibody being developed as a long-term prophylactic treatment for patients with HAE. Results from the trial, the first to investigate targeting activated Factor XII (FXIIa) to prevent HAE attacks, showed that once-monthly subcutaneous injections of garadacimab significantly reduced the attack rate compared to placebo.
“Targeting FXIIa and the HAE cascade from the start, as opposed to intervening downstream, is an innovative treatment approach that could help stop the process in its tracks,” says Dr. Timothy Craig, Tenured Professor of Medicine, Pediatrics and Biomedical Sciences at Penn State University, United States, and Principal Investigator of the study. “The Phase 3 data we are presenting support the potential use of garadacimab as a prophylactic therapy for HAE.”
Key Data from the Phase 3 VANGUARD Trial
During the double-blind, randomized, placebo-controlled, multicenter, parallel-group study, patients taking once monthly garadacimab (n=39) experienced a statistically lower monthly attack rate versus placebo (n=24) (p< 0.001), resulting in a mean attack rate reduction of 86.5% versus placebo, and a median attack rate reduction of 100% versus placebo. The mean attack rate reduction compared with placebo after adjusting for baseline attack rate was 89.2%.
Overall, during the six-month trial, a majority (61.5%) of patients taking garadacimab were attack-free, whereas no patients on the placebo arm were attack-free; 74.4% of patients taking garadacimab achieved ≥90% attack reduction versus the run-in period.
The study also showed that garadacimab demonstrated a favorable safety and tolerability profile. There were no adverse events that led to treatment discontinuation. Five injection site reactions, all mild, were reported in two (5.1%) patients treated with garadacimab and three patients (12%) on placebo.
“The data being shared at AAAAI showcase the efficacy and safety profile of garadacimab administered as a convenient monthly subcutaneous injection. The clinical trial results support garadacimab as a novel, first-in-class potential treatment that could offer a significant benefit to patients with HAE,” says Catherine Milch, Vice President R&D Immunology, CSL. “Garadacimab represents the next chapter in delivering on our promise to bring disruptive innovation and treatment options to patients living with rare diseases.”
Based on the full study data, which are consistent with the positive top-line results announced in August 2022, CSL plans regulatory submissions to global health authorities later this calendar year for approval of garadacimab.
About the Pivotal Phase 3 VANGUARD Trial
The multicenter, randomized, double-blind, parallel-group VANGUARD trial evaluated the efficacy and safety of garadacimab, an investigational first-in-class monoclonal antibody, as a prophylactic treatment for patients with HAE. Patients aged 12 years and older with HAE type I or II underwent screening and a run-in study period to verify a baseline attack rate. Patients were randomized 3:2 to receive a loading dose of 400mg followed by 200 mg of garadacimab monthly (n=39) or volume-matched placebo monthly (n=25) subcutaneously. After the six-month treatment period, patients were given the opportunity to continue into the open-label extension study, which is currently ongoing.
The ongoing open-label extension of the Phase 3 VANGUARD study evaluates the long-term safety and efficacy of garadacimab (200 mg monthly) in patients with HAE.
(Source: CSL Behring)