FDA approves garadacimab-gxii to prevent HAE attacks in patients aged 12 years, older | Image credit: Contemporary Pediatrics

The FDA has approved, for patients aged 12 years and older, CSL's garadacimab-gxii (Andembry) to prevent attacks of hereditary angioedema (HAE), according to a press release from the company. With the decision, the Xlla-targeting, prophylactic monoclonal antibody is indicated for adult and pediatric patients aged 12 years and older.¹

Approval was based on data from the phase 3 VANGUARD trial to evaluate the efficacy and safety of garadacimab-gxii. According to CSL, the double-blind, randomized, placebo-controlled, multicenter, and parallel-group study featured 39 patients taking once-monthly garadacimab-gxii. With data announced in February 2023, the garadacimab-gxii group experienced a statistically lower monthly attack rate compared to placebo (n = 24 [P < 0.001]), which resulted in a mean attack reduction of 86.5% compared to placebo. Additionally, a median attack rate reduction of more than 99% was observed for the treatment group compared to placebo.^1,2

Timothy Craig, DO, a tenured professor of Medicine, Pediatrics, and Biomedical Sciences at Penn State University, and principal investigator of VANGUARD, stated:

"We've made significant progress in treating hereditary angioedema, yet many patients still experience painful and sometimes life-threatening HAE attacks and require frequent injections to manage them," he said in a press release. "We now have a new option to manage this condition through a new target, as it allows us for the first time to inhibit the top of the HAE cascade by targeting factor XIIa."¹

In an ongoing open-label extension study (median garadacimab-gxii exposure of 13.8 months), an interim analysis demonstrated that garadacimab-gxii has a favorable long-term safety profile and provides sustained reduction in HAE attacks. Injection-site reactions were reported in 24 (14%) of patients.

"[Garadacimab-gxii], the first monoclonal antibody discovered and developed entirely by CSL, offers people living with this life-threatening condition long-term control over their disease along with a convenient administration method," said Bill Mezzanotte, MD, Executive Vice President, Head of R&D, CSL. "[Garadacimab-gxii] underscores our long-standing and enduring commitment to better the lives of the patients we serve, including those suffering with HAE. I'd like to thank all the physicians, patients and my colleagues who contributed to this exciting milestone for HAE patients and CSL."

Other HAE FDA pipeline news

On June 13, 2025, the FDA announced it will not meet the June 17, 2025, target action date to make a decision regarding KalVista Pharmaceuticals' sebetralstat to treat HAE in patients aged 12 years and older, with the federal agency having cited a heavy workload and limited resources, according to KalVista.³

The federal agency did not request additional data or studies and has not raised any concern about the safety, efficacy, or approvability of sebetralstat.

A new drug application (NDA) for sebetralstat was accepted by the FDA on September 3, 2024, to treat HAE attacks in adult and pediatric patients aged 12 years and older. The NDA for the novel, investigational, oral plasma inhibitor for on-demand treatment of HAE was submitted based on data from the phase 3 KONFIDENT clinical trial, as well as the KONFIDENT-S open-label extension trial.

Click here for more details on sebetralstat, including an updated timeline for potential approval.

References:

1. 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. CSL. Press release. June 16, 2025. Accessed June 17, 2025. https://www.prnewswire.com/news-releases/us-food-and-drug-administration-approves-csls-andembry-garadacimab-gxii-the-only-prophylactic-hereditary-angioedema-hae-treatment-targeting-factor-xiia-with-once-monthly-dosing-for-all-patients-from-the-start

2. CSL's phase 3 study shows first-in-class garadacimab provides patients with significant HAE attack prevention with monthly dosing. CSL. Press release. February 26, 2023. Accessed June 17, 2025. https://newsroom.csl.com/News-Releases?item=123049

3. Fitch J. FDA will not meet original PDUFA date for sebetralstat to treat HAE. Contemporary Pediatrics. June 16, 2025. Accessed June 17, 2025. https://www.contemporarypediatrics.com/view/fda-will-not-meet-original-pdufa-data-for-sebetralstat-to-treat-hae