Data from the VANGUARD phase 3 trial demonstrated that monthly administration of garadacimab significantly reduced hereditary angioedema (HAE) attacks in patients aged 12 or more years compared with placebo. The results, published in The Lancet, also showed garadacimab to have an acceptable safety profile.

“In a randomized, placebo-controlled phase 2 trial, garadacimab significantly reduced HAE attack rate compared with placebo through 12 weeks and provided the first clinical evidence of FXIIa inhibition as a novel strategy for HAE prophylaxis,” the authors wrote. “Here, the efficacy and safety of subcutaneous garadacimab were investigated in a 6-month, randomized, double-blind, placebo-controlled, pivotal phase 3 trial (VANGUARD) in patients with type I/II HAE.”

VANGUARD was a global trial conducted between January 27, 2021, and June 7, 2022, that included 76 patients aged 12 or more years with HAE type 1 or 2. The efficacy and safety of 2 initial subcutaneous injections of 200 mg garadacimab followed by once-monthly 200 mg garadacimab were investigated.

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The primary outcome measure was the time-normalized number of HAE attacks over a 6-month period, and the main secondary endpoints were the percentage reduction in attacks vs placebo, the number of patients who were attack-free at day 91, and the percentage rating the therapy as “good or better” at the 6-month mark.

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The results showed that garadacimab led to significant and meaningful reductions in attacks compared with placebo, all primary endpoints were met, and no significant safety issues were observed. Nearly two-thirds of the participants were attack-free at 6 months, while none in the placebo arm were attack-free. The treatment also reduced the severity of attacks and was rated as “excellent” by 65.8% of the patients and as “good or better” by 81.6%.

Garadacimab, therefore, shows significant potential as an effective prophylactic therapy option for HAE in this patient population.


Craig T, Reshef A, Li HH, et al. Garadacimab, a factor XIIa inhibitor for hereditary angioedema prevention (VANGUARD Study). The Lancet. Published online January 26, 2023. doi:10.2139/ssrn.4336148