1. Compared to placebo, monthly garadacimab significantly reduced the number of hereditary angioedema attacks per month.
2. Overall, garadacimab was well-tolerated, with the most common adverse events being upper respiratory tract infections, nasopharyngitis, and headaches.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Hereditary angioedema (HAE) is a rare genetic disorder that is characterized by recurring episodes of swelling in various parts of the body, including the face, throat, and abdomen. Garadacimab is a monoclonal IgG4 antibody against Factor XIIa that has been shown to reduce the number of hereditary angioedema attacks compared to placebo in previous studies. In this phase 3 study, participants with type 1 or type 2 hereditary angioedema were randomized to a 6-month treatment regimen of subcutaneous garadacimab or placebo. During the treatment period, there were significantly fewer attacks per month in the treatment group compared to the placebo group. The most common treatment-related adverse events were upper respiratory tract infections, nasopharyngitis, and headaches. Limitations of this study include the short treatment period of 6 months. Nevertheless, this study demonstrates the efficacy of prophylactic monthly subcutaneous garadacimab in reducing hereditary angioedema attacks.
Click to read the study in The Lancet
Relevant Reading: Effect of Lanadelumab Compared With Placebo on Prevention of Hereditary Angioedema Attacks
In-Depth [randomized controlled trial]: VANGUARD was a randomized, placebo-controlled, phase 3 trial of subcutaneous garadacimab for the treatment of type 1 or type 2 hereditary angioedema. Eligible patients were aged 12 years or older with a laboratory-confirmed diagnosis of type 1 or type 2 hereditary angioedema. Patients must have had at least 3 months before screening and were required to stop using long-term prophylactic treatment during the study. The garadacimab regimen consisted of an initial loading dose of two 200 mg subcutaneous injections followed by 200 mg once monthly maintenance doses for a 6-month treatment period.
A total of 64 patients were randomized 3:2 to either subcutaneous garadacimab (n = 39) or placebo (n = 25). 59% of the participants were female. All 39 patients completed treatment with garadacimab. Three patients withdrew from the placebo group due to a lack of efficacy (n = 1) and attacks (n = 2). The mean number of hereditary angioedema attacks per month was significantly lower in the garadacimab group (0.27, 95% CI 0.05 to 0.49) compared to placebo (2.01, 1.44 to 2.57; p<0.0001) during the 6-month treatment period, which corresponds to a percentage difference in means of -87% (-96 to -58, p<0.0001). There were 25 (64%) treatment-emergent adverse events in the garadacimab group compared to 15 (60%) in the placebo group. Upper-respiratory tract infections, nasopharyngitis, and headaches were the most common treatment-emergent adverse events.
Image: PD
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