Garadacimab, XIIa inhibitor, receives FDA and EMA Filing acceptance for hereditary angioedema
USA: Garadacimab, a first-in-class factor XIIa inhibitor, has received the Food and Drug Administration (FDA) and European Medicines Agency (EMA) filing acceptance as a prophylactic treatment for hereditary angioedema (HAE). If approved, garadacimab would become the first treatment for HAE in the US and EU to target activated Factor XII (FXIIa).
A global biotechnology company CSL has announced that the US FDA has accepted its Biologics License Application (BLA) for garadacimab (CSL312) as a once-monthly prophylactic treatment for HAE. The company also announced that the EMA has accepted the submission for the Marketing Authorization Application (MAA) for garadacimab.
Orphan-drug designation for garadacimab as a therapy for hereditary angioedema has already been granted by both the FDA and the EMA.
Garadacimab is a novel, first-in-class, recombinant monoclonal antibody that targets activated FXII. FXIIa is a plasma protein that initiates the kallikrein-kinin cascade of HAE attacks. By targeting FXIIa, garadacimab inhibits this cascade at the top compared to HAE therapies targeting downstream mediators.
The MAA and BLA are supported by data from the multicenter, pivotal, randomized, parallel-group, double-blind VANGUARD trial, which evaluated the safety and efficacy of garadacimab as a prophylactic treatment for HAE patients. The findings from the VANGUARD trial were published in The Lancet in the April 2023 issue. The ongoing open-label extension of the VANGUARD study evaluates the long-term efficacy and safety of garadacimab (200 mg monthly) in patients with HAE.
Study participants were randomly assigned in a ratio of 3:2 to receive garadacimab (n=39) 400mg subcutaneously (SC) as a loading dose on day one followed by 200mg SC once monthly or placebo (n=25) for 6 months. The primary endpoint was the time-normalized number of HAE attacks per month during the treatment period.
The trial showed a significantly lower number of investigator-confirmed HAE attacks per month in patients treated with garadacimab vs those who received placebo (0.27 versus 2.01). This finding corresponded to a mean attack rate reduction of 87%. The median number of HAE attacks per month was 0 in the garadacimab arm and 1.35 in the placebo arm.
Hereditary angioedema is a rare, genetic, and potentially life-threatening condition that causes debilitating, painful and unpredictable episodes of swelling of the larynx, abdomen, face, and extremities, among other body areas.
Garadacimab, a novel Factor XIIa-inhibitory monoclonal antibody (anti-FXIIa mAb), has completed Phase 3 clinical development as a potential new type of once-monthly subcutaneous prophylactic treatment for attacks related to HAE, a form of bradykinin-mediated angioedema. Garadacimab uniquely inhibits FXIIa, the plasma protein.
If approved, patients will have the benefit of an auto-injector (pre-filled pen) for convenient administration.
CSL is also investigating garadacimab for other indications beyond HAE, including idiopathic pulmonary fibrosis, where FXIIa inhibition may play an important role in improving clinical outcomes.
"We believe that garadacimab has the potential to become a promising therapy in the prevention of HAE attacks and we look forward to working closely with global health regulators throughout the review process," according to Emmanuelle Lecomte Brisset, Pharm D, Senior Vice President and Global Head of Regulatory Affairs at CSL.
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