FDA Approves ANDEMBRY (garadacimab-gxii) The First Once-Monthly Prophylactic HAE Therapy Targeting Factor XIIa
CSL a leading biotechnology company with a strong track record of developing innovative medicines for patients with rare and serious disorders, today announced that the U.S. Food and Drug Administration (FDA) has approved ANDEMBRY® (garadacimab-gxii) for prophylactic use in the prevention of attacks in patients with hereditary angioedema (HAE) who are 12 years of age or older. This significant approval marks a major milestone in the care of individuals living with this rare, chronic, and potentially life-threatening condition.
ANDEMBRY is a first-of-its-kind prophylactic therapy that directly targets and inhibits plasma kallikrein’s initiation cascade by binding to and inhibiting factor XIIa — a key plasma protein that plays a pivotal role in triggering attacks in people with HAE. This unique approach prevents attacks from occurring before they start, offering patients a new opportunity to manage their condition while reducing the immense disease burden. Importantly, ANDEMBRY is the only prophylactic treatment that offers convenient once-monthly subcutaneous administration with a citrate-free formulation — a feature designed to ease administration, improve tolerability, and enable greater independence for patients.
The administration process itself can be completed in 15 seconds or less using a convenient autoinjector, adding to its appeal for patients who wish to avoid frequent, cumbersome, or painful infusion schedules. The ability for patients to self-administer their medication at home further underscores the significance of ANDEMBRY in improving their daily lives.
Hereditary angioedema (HAE) is a rare, autosomal dominant, and potentially life-threatening condition that occurs in roughly 1 in 50,000 people, regardless of ethnic group or geographic location. HAE attacks typically manifest as sudden and severe swelling of the face, limbs, gastrointestinal tract, and upper airways, causing immense distress and, in some cases, threatening the patient’s ability to breathe. Because attacks are unpredictable and painful, the disease can undermine a patient’s physical health, mental well-being, employment, education, relationships, and overall quality of life.
“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 Research & Development at CSL. “ANDEMBRY underscores our long-standing and enduring commitment to improving the lives of the patients we serve, including those suffering with hereditary angioedema. I’d like to thank all the physicians, patients, and my colleagues who contributed to this significant milestone for the HAE community and for CSL.”
The approval by the FDA is supported by data from the pivotal, placebo-controlled VANGUARD Phase 3 trial, which was designed to evaluate both the efficacy and safety profile of ANDEMBRY. The results — previously published in The Lancet in April 2023 — highlight the impressive benefits ANDEMBRY can provide:
- 62% of ANDEMBRY-treated patients remained attack-free during the treatment period.
- The therapy resulted in a greater than 99% median reduction in attacks and a least squares mean of 89.2% when directly comparing ANDEMBRY to placebo.
- There was a 99% or greater medial reduction in attacks requiring on-demand therapy — alongside an 88% mean reduction — demonstrating its ability to ease disease severity.
- Furthermore, ANDEMBRY attained more than 99% medial reduction and a 90% mean reduction in attacks classified as moderate or severe — reflecting its potent ability to ease the most severe attacks.
The most frequently reported adverse reactions (with an incidence greater than or equal to 7%) in the pivotal trial were nasopharyngitis and abdominal pain. Importantly, data from the open-label extension study (with a medial ANDEMBRY exposure of 13.8 months) further demonstrated a favorable long-term safety profile, with sustained reductions in attack frequency over time. Injection-site reactions — including bruising, redness, hematoma, itchiness, and urticaria — were documented in 23 (14%) patients across both phases of the study. Overall, the therapy was well-tolerated, adding credence to its strong safety profile alongside its potent efficacy.
“We’ve made significant progress in treating hereditary angioedema, yet many patients still experience painful and sometimes life-threatening attacks and require frequent injections to manage them,” said Dr. Tim Craig, Professor of Medicine, Pediatrics and Biomedical Sciences at Penn State University. “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.”
“ANDEMBRY, a novel once-monthly subcutaneous treatment that inhibits factor XIIa, is a welcome addition to the HAE treatment landscape,” said Anthony J. Castaldo, President and Chief Executive Officer of the US Hereditary Angioedema Association (HAEA) and HAE International. “People with HAE now have another choice for lessening the burden associated with this lifelong condition and for experiencing life to the fullest — which is a shared, universal goal for the community.”
This regulatory approval by the FDA marks another crucial step toward making ANDEMBRY available to patients across the globe. The treatment was previously approved in Australia, the United Kingdom (UK), the European Union (EU), Japan, Switzerland, and the United Arab Emirates (UAE). Shortly, it will be made available to patients in the USA, with commercial launch expected before the end of June.
Healthcare providers and patients who wish to learn more about ANDEMBRY or explore their options for accessing the therapy are encouraged to use ANDEMBRY ConnectSM — a comprehensive support platform designed to aid both patients and their care teams with education, financial assistance, and other resources.
