FDA

Andembry OK’d for prophylaxis of hereditary angioedema

June 23, 2025

Brand name: Andembry

Generic name: garadacimab-gxii

Manufacturer: CSL

Approval date: June 16, 2025

FDA approved Andembry (garadacimab-gxii), an activated Factor XII inhibitor, for prophylactic use to prevent attacks of hereditary angioedema (HAE) in adult and pediatric patients ≥12 years of age.

Efficacy

Approval was supported by data from the placebo-controlled phase 3 VANGUARD trial (NCT04656418) involving 64 adult and pediatric patients ≥12 years of age with Type I or Type II HAE who experienced at least 2 investigator-confirmed HAE attacks over a 2-month period prior to treatment with Andembry or placebo. Patients were randomized in a 3:2 ratio to receive an initial loading dose of Andembry 400 mg SC followed by a maintenance dose of 200 mg every month, or matched placebo. Patients were required to discontinue other prophylactic HAE medications prior to entering the study. All patients were allowed to use on-demand medications for the treatment of HAE attacks during the study.

The primary endpoint was the monthly HAE attack rate at 6 months (number of investigator-confirmed HAE attacks per month). Andembry reduced the monthly attack rate by a relative 89.2% compared with placebo over the 6-month period (mean, 0.22 vs. 2.01 per month, P<0.0001).

The monthly rate of HAE attacks requiring on-demand therapy and the monthly rate of moderate or severe HAE attacks were secondary endpoints. There was a 91.2% reduction with Andembry relative to placebo in the monthly rate of HAE attacks requiring on-demand therapy and a 93.6% reduction with Andembry relative to placebo in the monthly rate of moderate or severe HAE attacks.

Additional secondary endpoints assessed the proportion of patients with a ≥50%, ≥70%, ≥90%, and 100% (attack-free) reduction in monthly HAE attack rate from the first dose through the end of the 6-month treatment period compared with the 2-month period prior to treatment. Attack rate reduction rates with Andembry vs. placebo were as follows:

• ≥50% reduction: 95% vs. 33%
• ≥70% reduction: 92% vs. 17%
• ≥90% reduction: 74% vs. 8%
• 100% reduction: 62% vs. 0%

A published interim analysis (October 2024) of an ongoing open-label extension study (median Andembry exposure of 13.8 months) showed that Andembry has a favorable long-term safety profile and provides sustained reductions in HAE attacks.

Safety

The most common adverse reactions overall (>7%) observed in the VANGUARD trial were nasopharyngitis and abdominal pain. In the pivotal trial and the open-label extension study, injection-site reactions (e.g., injection-site bruising, injection-site erythema, injection-site hematoma, injection-site pruritus, injection-site urticaria) were reported in 23 (14%) patients.

Recommended dose

The recommended dosage of Andembry is an initial loading dose of 400 mg (two 200 mg injections) SC followed by a maintenance dosage of 200 mg once monthly.

Sources:

US Food and Drug Administration approves CSL’s Andembry® (garadacimab-gxii), the only prophylactic hereditary angioedema (HAE) treatment targeting Factor XIIa with once-monthly dosing for all patients from the start. [News release]. 2025. https://newsroom.csl.com/2025-06-16-U-S-Food-and-Drug-Administration-Approves-CSLs-ANDEMBRY-R-garadacimab-gxii-,-the-Only-Prophylactic-Hereditary-Angioedema-HAE-Treatment-Targeting-Factor-XIIa-with-Once-Monthly-Dosing-for-All-Patients-From-the-Start

ANdembry (garadacimab-gxii) [package insert]. CSL. https://labeling.cslbehring.com/PI/US/Andembry/EN/Andembry-Prescribing-Information.pdf Revised June 2025. Accessed June 20, 2025.