The U.S. Food and Drug Administration has approved ANDEMBRY® (garadacimab-gxii), marking a significant advancement in hereditary angioedema (HAE) prevention as the only treatment targeting factor XIIa for prophylactic use. Developed by global biotechnology leader CSL, ANDEMBRY offers once-monthly dosing for adult and pediatric patients aged 12 years and older, representing the first monoclonal antibody discovered and developed entirely by the company.
Novel Mechanism of Action
ANDEMBRY distinguishes itself through its unique targeting of factor XIIa, a plasma protein that plays a key role in HAE attacks. By inhibiting factor XIIa, ANDEMBRY blocks the top of the HAE cascade, preventing the cascade of events that lead to angioedema attacks. This approach differs from other HAE therapies that target downstream mediators in the pathway.
"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," said Dr. Tim Craig, Professor of Medicine, Pediatrics and Biomedical Sciences at Penn State University.
Pivotal Trial Results
The FDA approval is supported by robust data from the Phase 3 VANGUARD trial, a multicenter, randomized, double-blind, parallel-group study published in The Lancet in April 2023. The trial evaluated 64 patients aged 12 years and older with HAE type I or II, randomized 3:2 to receive either ANDEMBRY (400 mg loading dose followed by 200 mg monthly) or placebo.
The pivotal study demonstrated remarkable efficacy outcomes:
- 62% of ANDEMBRY-treated patients remained completely attack-free throughout the six-month treatment period
- HAE attacks were reduced by a median of more than 99% and a least squares mean of 89.2% compared to placebo
- More than 99% median reduction and 88% mean reduction in HAE attacks requiring on-demand therapy
- More than 99% median reduction and 90% mean reduction in moderate or severe attacks
Safety Profile and Long-term Data
The most common adverse reactions in the pivotal trial (incidence ≥7%) were nasopharyngitis and abdominal pain. Injection-site reactions, including bruising, erythema, hematoma, pruritus, and urticaria, were reported in 23 (14%) patients across the pivotal trial and open-label extension study.
A published interim analysis from October 2024 in Allergy journal of the ongoing open-label extension study, with a median ANDEMBRY exposure of 13.8 months, confirmed the treatment's favorable long-term safety profile and sustained reductions in HAE attacks.
Addressing Unmet Medical Need
HAE is a rare, chronic, and potentially life-threatening genetic disorder that occurs in approximately 1 in 50,000 people of any ethnic group. The condition is characterized by recurrent and unpredictable attacks of angioedema that can affect multiple body sites, including the abdomen, larynx, face, and extremities. HAE attacks involving the face or throat can result in airway closure, asphyxiation, and death if left untreated.
"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.
Treatment Administration and Availability
ANDEMBRY is administered as a subcutaneous self-injection delivered in 15 seconds or less via an autoinjector with a citrate-free formula. The treatment offers the convenience of once-monthly dosing from the start for all patients, addressing the burden of frequent injections that many HAE patients currently experience.
CSL Behring will launch ANDEMBRY commercially immediately, with availability before the end of June. The approval expands CSL's HAE franchise and represents another step toward global availability, following recent approvals in Australia, the United Kingdom, European Union, Japan, Switzerland, and United Arab Emirates.
"ANDEMBRY, a novel once-monthly subcutaneous treatment that inhibits factor XIIa, is a welcome addition to the HAE treatment landscape," said Anthony J. Castaldo, CEO and Chairman of the Board, US HAE Association and HAE International. "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."
Healthcare professionals and patients can access comprehensive support through ANDEMBRY ConnectSM by calling 844-423-4273 or visiting www.ANDEMBRY.com.
