CSL's Andembry (Garadacimab) Approved in Europe and UK for Hereditary Angioedema
Key Insights
The European Commission and the MHRA have approved CSL (search)'s Andembry (garadacimab) for preventing hereditary angioedema (search) (HAE) attacks in patients aged 12 and older.
Andembry, a Factor XIIa (search)-inhibitory monoclonal antibody, offers a novel approach by targeting the initiation of the angioedema cascade with a once-monthly subcutaneous injection.
Clinical trials, including the VANGUARD trial, demonstrated that Andembry significantly reduced HAE attack rates and achieved attack-free status in a substantial portion of patients.
CSL Behring's Andembry (garadacimab) has received approvals from both the European Commission (EC) and the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK for the prevention of recurrent hereditary angioedema (search) (HAE) attacks in patients aged 12 years and older. This decision marks a significant advancement in the management of HAE, offering a novel therapeutic approach.
Andembry is a recombinant monoclonal antibody that targets Factor XIIa (search), a plasma protein crucial in initiating the cascade of events leading to angioedema. Administered as a once-monthly subcutaneous injection via a pre-filled pen, Andembry can be self-administered by patients or caregivers following proper training.
The approvals are based on data from the Phase 3 VANGUARD trial and its open-label extension study. The VANGUARD trial demonstrated a significant reduction in HAE attack rates, from a mean of 2.01 attacks per month at baseline to 0.27 per month after six months of treatment. Notably, 62% of patients treated with Andembry achieved attack-free status during the treatment period. Furthermore, the drug reduced the median number of HAE attacks to zero and lowered the mean number of HAE attacks per month by 86.5% compared to placebo.
Clinical Efficacy and Safety
The VANGUARD trial, a pivotal international Phase 3 study, enrolled 64 HAE patients aged 12 and older. Results published in The Lancet in April 2023 highlighted the efficacy and safety of garadacimab. An ongoing open-label extension study further supports these findings, with an interim analysis showing a 95% reduction in swelling attack rates and more than half of patients being attack-free with a median garadacimab exposure of 13.8 months. The most common side effects reported were injection site reactions.
Mechanism of Action
Andembry's unique mechanism of action involves inhibiting plasma protein FXIIa, preventing the initiation of the cascade that leads to edema formation. This contrasts with other HAE therapies that target downstream mediators. By blocking the activation of FXII, Andembry aims to provide more effective and sustained control over HAE attacks.
Impact on Patients
HAE is a rare, genetic condition affecting approximately 1 in 50,000 people, characterized by recurrent and unpredictable swelling attacks that can affect various body parts, including the abdomen, face, and airways. These attacks can be painful and, in severe cases, life-threatening. The availability of Andembry offers a new option for patients to manage their condition and improve their quality of life.
Henrik Balle Boysen, President of HAE International, commented that Andembry, as a novel once-monthly subcutaneous treatment that inhibits activated Factor XII, is a welcome addition to the HAE treatment landscape, offering people with HAE another choice for lessening the burden associated with this lifelong condition.
Regulatory Status and Availability
With approvals secured in the UK and Europe, Andembry is under regulatory review in the United States, Japan, Switzerland, and Canada. CSL Behring will work to make Andembry available for eligible patients following access and reimbursement negotiations.