Garadacimab significantly reduces hereditary angioedema attack rates
Click Here to Manage Email Alerts
SAN ANTONIO — Garadacimab significantly reduced attack rates among patients with hereditary angioedema and was well tolerated, according to an abstract presented at the American Academy of Allergy, Asthma & Immunology Annual meeting.
Led by Timothy Craig, DO, clinical researcher, department of medicine, pediatrics and biomedical sciences, Pennsylvania State University, the randomized phase 3 trial enrolled 63 patients aged 12 years and older with type I or II hereditary angioedema.
“We know that people with hereditary angioedema have a significant impact on their quality of life,” Craig said during his presentation. “Thus, this study is very important.”
Garadacimab (CSL Behring) is a fully human immunoglobulin G4 monoclonal antibody that targets activated factor XII to prevent hereditary angioedema (HAE) attacks.
The treatment cohort included 39 patients (mean age, 43.3 years; standard deviation (SD), 17.45; 61.5% female) with one or more HAE attacks per month during the 2-month run-in treated with garadacimab administered subcutaneously, beginning with a 400 mg dose followed by 200 mg doses each month for 6 months.
“Efficacy was rapid in onset,” Craig said.
The placebo cohort included 25 patients (mean age, 37.8; SD, 12.8; 56% female) who also had one or more attacks per month during the run-in.
HAE attack rates per month during the run-in period included a mean of 2.52 (95% CI, 2.13-2.91) and a median of 2.23 (interquartile range [IQR], 1.4) for the placebo group and a mean of 3.07 (95% CI, 2.41-3.73) and a median of 2.61 (IQR, 1.75) for the treatment group.
Through day 182 of treatment, patients on garadacimab experienced an 86.5% (95% CI, 57.8%-95.7%) reduction in attack rate compared with the group on placebo. Mean monthly attack rates included 0.22 (95% CI, 0.11-0.47) for the treatment group and 2.07 (95% CI, 1.49-2.87) for the placebo group after adjustment for baseline attack rates, for an 89.2% (95% CI, 75.6%-95.2%) reduction.
Median attack rates per month included 0.00 (IQR, 0.31) for the treatment group, which the researchers called a 100% reduction in median HAE attack rate, and 1.35 (IQR, 2.2) for the placebo group.
Also, 61.5% (n = 24) of the treatment group was free of attacks during the 6-month study period, with 74.4% achieving a 90% reduction or higher in attacks compared with the run-in period. Two (8.3%) of the patients in the placebo group achieved a 90% or greater reduction in attacks, and none of them were attack-free, during the 6-month study period.
Times to first attack included 72 days or longer for 75% of the treatment group and 5 days or longer for 75% of the placebo group.
“There was a significant decrease of on-demand need for therapy in those who were on garadacimab,” Craig said. “There is increased satisfaction with therapy.”
Total mean scores on the Angioedema-Quality of Life scale improved by a reduction of –26.5 (SD, –17.9) points from baseline to day 182 for the treatment group and –2.2 (SD, –19.1) for the placebo group as well.
The researchers further reported 129 treatment-emergent adverse events, with 62.5% (n = 40) of patients experiencing one or more, including 64.1% of the treatment group and 60% of the placebo group. There were no deaths or adverse events leading to discontinuation.
One laryngeal attack was considered serious but not related to treatment, and the patient spent the night in the hospital for observation. Also, there was no anaphylaxis, thromboembolic events or abnormal bleeding events.
The most common events were injection-site reactions, with four (6%) patients experiencing five incidents, including three in the placebo group and two in the treatment group. Upper respiratory tract infections, nasopharyngitis and headache were common as well.
“Thus, not only is the drug effective, but it is also tolerated well with few injection site reactions and no abnormal special interest adverse events,” Craig said.