The FDA has approved CSL’s Andembry (garadacimab-gxii), a first-in-class, once-monthly subcutaneous (SC) treatment for the prevention of hereditary angioedema (HAE) attacks in patients aged 12 years and older. According to the company, Andembry is the only prophylactic HAE therapy that targets factor XIIa, inhibiting the top of the HAE inflammatory cascade. Additionally, the treatment is self-administered in under 15 seconds via autoinjector and marks CSL’s first fully discovered and developed monoclonal antibody. Approval was based on pivotal results from the Phase III VANGUARD trial.¹

How Does Andembry Offer a New Approach to Preventing HAE Attacks?

"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, EVP, head, R&D, CSL, in a press release. "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."

VANGUARD Trial Design and Key Findings

• The multicenter, randomized, double-blind, parallel-group VANGUARD trial evaluated the efficacy and safety of Andembry compared to placebo in 64 patients with HAE type I or II.
• Patients were randomly assigned in a 3:2 ratio to receive a loading dose of 400 mg followed by 200 mg of SC Andembry or placebo.
• At six months, patients were given the chance to continue into the open-label extension study, currently in progress.
• The primary endpoint of the study was the rate of HAE during the treatment period.
• Results showed that Andembry demonstrated a median >99% reduction in HAE attacks, with 62% of treated patients experiencing no attacks throughout the study.
• Patients treated with Andembry achieved an 88% mean reduction in HAE attacks requiring on-demand therapy compared to placebo.
• There was a 99% median reduction as well as a 90% mean reduction in moderate or severe attacks compared to placebo.

Safety Profile and Adverse Events

• Common adverse events included nasopharyngitis and abdominal pain.
• Additionally, the safety profile was reported to be favorable in this indication.
• In the extension study, injection-site reactions were reported in 14% of patients, which included injection-site bruising, injection-site erythema, injection-site hematoma, injection-site pruritus, and injection-site urticaria.¹

Expert Perspectives

"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, professor of medicine, pediatrics, and biomedical sciences, Penn State University, in the 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."

Epidemiology of HAE

According to a study published in the National Center for Biotechnology Information the global estimated prevalence of HAE is one in 50,000, ranging from 1:10,000 to 1:150,000. Type I is estimated to account for 80% to 85% of all HAE, while type II consists of the remaining 15% to 20%.²

A Milestone for the HAE Community

"Aendembry, a novel once-monthly subcutaneous treatment that inhibits factor XIIa, is a welcome addition to the HAE treatment landscape," said Anthony J. Castaldo, CEO, chairman of the board, US HAE Association, HAE International, in the press release. "People with HAE now have another choice for lessening the burden associated with this lifelong condition and realizing the community's shared goal of experiencing life to the fullest."

References

1. U.S. 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. PR Newswire. June 15, 2025. Accessed June 17, 2025. https://prnmedia.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. Hereditary angioedema: epidemiology, management, and role of icatibant. PubMed. Accessed June 17, 2025. https://pmc.ncbi.nlm.nih.gov/articles/PMC3647445/#:~:text=The%20estimated%20prevalence%20of%20HAE%20is%201%20in%2050%2C000%2C%20with,:10%2C000%20to%201:150%2C000.&text=HAE%20has%20been%20reported%20in,remaining%2015%25%20to%2020%25.