FDA Approves Garadacimab-gxii in Hereditary Angioedema

The FDA granted approval to CSL’s garadacimab-gxii (Andembry), a first-in-class factor XII (FXIIa) inhibitor for patients with hereditary angioedema (HAE).¹

FDA granted approval to CSL’s garadacimab-gxii for patients with hereditary angioedema.| Image Credit: Nirusmee - stock.adobe.com

In December 2023, CSL announced that the FDA and European Medicines Agency had accepted regulatory submissions for garadacimab-gxii as a once-monthly prophylactic treatment for HAE.² The approval is supported by findings from the pivotal VANGUARD trial (NCT04656418), presented during the 2023 American Academy of Allergy, Asthma & Immunology Annual Meeting in San Antonio, Texas.³ This was a phase 3 randomized, double-blind, placebo-controlled, multicenter study, which evaluated the efficacy and safety of garadacimab.

"Andembry, 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, in a statement.¹ "Andembry 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."

Over the 6-month treatment period, patients treated with garadacimab experienced a significantly lower mean number of investigator-confirmed HAE attacks per month (0.27; 95% CI, 0.05-0.49) compared with those on placebo (2.01; 95% CI, 1.44-2.57), reflecting an 87% reduction in attack frequency (P < .0001).⁴ Median (IQR) monthly attacks were 0 (0.00-0.31) for garadacimab vs 1.35 (1.00-3.20) for placebo.

Garadacimab also significantly reduced moderate or severe attacks and the need for rescue medication, and 81.6% of patients rated their response as “good” or better compared with 33.3% on placebo.³ Safety findings were favorable, with similar rates of treatment-emergent adverse events in both groups and no bleeding or thrombotic events. The most common adverse effects included upper respiratory infections, nasopharyngitis, and headache.

"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," said Tim Craig, DO, professor of medicine, pediatrics and biomedical sciences at Penn State University, in a statement.¹ "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."

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. News 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-302483058.html

2. CSL's garadacimab, a first-in-class factor XIIa inhibitor, receives FDA and EMA filing acceptance. CSL. News release. December 14, 2023. Accessed June 16, 2025. https://newsroom.csl.com/2023-12-14-CSLs-Garadacimab,-a-First-in-Class-Factor-XIIa-Inhibitor,-Receives-FDA-and-EMA-Filing-Acceptance

3. The Lancet publishes pivotal phase 3 data on CSL's first-in-class garadacimab for HAE. CSL. News release. March 1, 2023. Accessed June 16, 2025. https://www.prnewswire.com/news-releases/the-lancet-publishes-pivotal-phase-3-data-on-csls-first-in-class-garadacimab-for-hae-301759437.html

4. Craig TJ, Reshef A, Li HH, et al. Efficacy and safety of garadacimab, a factor XIIa inhibitor for hereditary angioedema prevention (VANGUARD): a global, multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. April 1, 2023. doi: 10.1016/S0140-6736(23)00350-1