Garadacimab showing safety in HAE patients with long-term use
Interim extension trial data might support approval review underway in US, EU
Garadacimab appears to be safe for long-term use as prophylaxis, or preventive treatment, reducing the frequency of swelling attacks in adults and adolescents with hereditary angioedema (HAE), according to an interim analysis of data from an ongoing Phase 3 extension study sponsored by its developer, CSL Behring.
Most adverse events in this open-label trial of garadacimab’s safety and efficacy were mild or moderate, and those related to the therapy mostly were injection site reactions, the researchers reported.
Used for one year or longer, “garadacimab has the potential to bring patients closer to achieving the HAE treatment goals of complete disease control and normalization of patients’ lives,” they wrote.
The potential therapy currently is under review for approval in the U.S. and the European Union.
Garadacimab is being given monthly to 161 HAE patients in extension trial
Findings were reported in the study, “Long-term safety and efficacy of garadacimab for preventing hereditary angioedema attacks: Phase 3 open-label extension study,” published in Allergy.
HAE is due to too much of the signaling molecule bradykinin causing fluid to leak from small blood vessels, leading to swelling under the skin or in mucous membranes throughout the body. Bradykinin is formed by the action of an enzyme called kallikrein.
In turn, kallikrein is formed when a clotting protein called factor XII (FXII) is activated, triggering a chain of events that lead to swelling. Unlike other medications for angioedema, which work further down that chain, garadacimab is designed to target activated FXII and shut down the triggering factor for the swelling.
In the placebo-controlled Phase 3 VANGUARD trial (NCT04656418), garadacimab led to a greater than 85% reduction in the number of monthly swelling attacks experienced by patients with HAE, ages 12 and older, with nearly two-thirds remaining free from swelling attacks over six months of treatment.
The ongoing and long-term extension study (NCT04739059) involves 161 patients who were either newly enrolled or had taken part in VANGUARD or an earlier Phase 2 study (NCT03712228). All are receiving garadacimab at a dose of 200 mg, given by a subcutaneous (under-the-skin) injection once monthly for at least 12 months.
Mild or moderate injection site reactions are common side effect of treatment
Its main goal is to watch for side effects that may occur with garadacimab for up to 45 months, or nearly four years. Treatment efficacy is being evaluated as secondary goals.
The interim analysis was done after a median 13.8 months, or slightly longer than one year. Nearly two-thirds of its patients (62.7%) were female, and the entire group’s mean age at entry was 42.3. Ten were adolescents, ages 12-17.
Most patients (83.6%) experienced at least one side effect, mainly mild or moderate in severity. Three patients (1.9%) experienced serious side effects — two cases of COVID-19 and one abdominal HAE attack — which were not considered to be related to garadacimab. There were no deaths during the study.
Side effects related to garadacimab were reported in 21 patients (13%), with injection-site reactions being the most common. One patient discontinued treatment due to a moderate injection-site reaction that occurred within 24 hours of the injection and resolved after 13 days.
“The safety profile reported here is generally consistent with that observed in the pivotal phase 3 (VANGUARD) study,” the researchers reported.
95% drop in monthly swelling attacks seen with garadacimab’s use
In line with earlier trial data, garadacimab resulted in a 95% reduction in swelling attacks compared with attacks during a run-in period prior to the study’s start. The mean number of monthly swelling attacks dropped from 3.57 to 0.16. This reduction was consistent over time, and similar in patients who were newly enrolled or had rolled over from previous studies.
More than half of the patients (59.6%) remained free from swelling attacks, and most (93.2%) rated their experience with the treatment positively, describing it as either good or excellent, “likely a reflection of the patients’ satisfaction with the durable efficacy of garadacimab in preventing attacks,” the researchers wrote.
“Our interim analysis indicates that garadacimab has a favorable safety profile suitable for long-term use and provides durable protection against HAE attacks, findings that are generally consistent with safety and efficacy data from previous studies,” they concluded.
The extension study is expected to conclude in late 2025.
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