CSL Gains FDA Approval for its Preventative HAE Treatment
The once-monthly injection, which is the first FDA-approved HAE treatment, was proven to significantly reduce HAE attacks in a Phase III trial and strengthens CSL’s presence in the competitive rare disease market.
Melbourne-based biotechnology company CSL has received U.S. FDA approval for garadacimab-gxii (ANDEMBRY), a first-in-class, once-monthly preventative treatment for hereditary angioedema (HAE). The regulatory decision was announced by the company in a June 16, 2025 press release (1).
HAE is a rare genetic disorder affecting an estimated 1 in 10,000 to 1 in 50,000 people. It is caused by a deficiency or dysfunction of the C1-inhibitor protein — responsible for regulating key biochemical pathways in the blood — with disruption leading to uncontrolled bradykinin production to trigger recurrent episodes of severe swelling (2). Symptoms can affect the face, abdomen, limbs, and airway. Abdominal attacks often cause intense pain, nausea, and vomiting, while swelling in the throat or face can obstruct the airway, posing a risk of asphyxiation if left untreated.
Garadacimab-gxii is the first HAE treatment to specifically target activated Factor XIIa (FXIIa) — the initiating protein that triggers the cascade leading to swelling attacks. Unlike existing therapies that act further downstream, garadacimab-gxii intervenes at the source, disrupting the pathway before symptoms can occur. Delivered via a 15-second self-administered subcutaneous autoinjector, a 400 mg loading dose is followed up by a 200 mg maintenance dose administered once per month.
"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 Dr. Tim Craig, Professor of Medicine, Pediatrics and Biomedical Sciences at Penn State University, in the company press release (1). "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.”
The FDA’s approval decision was based on data from the Phase III VANGUARD trial. The trial demonstrated that once-monthly dosing of garadacimab-gxii reduced HAE attacks by a median of more than 99%, with 62% of participants remaining entirely attack-free during the six-month study period. The therapy’s safety profile was comparable to placebo; no thrombotic or bleeding events reported, with the most commonly reported side effects being headaches, abdominal pain, and nasopharyngitis.
Garadacimab-gxii enters a competitive HAE market that includes established therapies such as Takeda’s subcutaneous lanadelumab-flyo (TAKHZYRO) and BioCryst’s oral berotralstat (ORLADEYO), while KalVista’s sebetralstat remains under regulatory review. CSL envisions garadacimab-gxii as part of a complementary regimen, with its once-monthly dosing offering a long-acting preventive option that may be paired with on-demand oral rescue therapies.
Analysts estimate that garadacimab-gxii’s combination of robust efficacy, favorable safety profile, and convenient monthly dosing could support global annual sales in the range of USD 500–700 million (3). In addition to the U.S., the therapy has already secured regulatory approval in the E.U., U.K., Japan, Australia, and Switzerland.
References
CSL. 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. Press Release, June 16, 2025.
HAEI. HAE is a Very Rare, Genetic Disease. Blog, April 3, 2025.
AInvest. A New Dawn for Rare Disease Therapies: CSL's ANDEMBRY Launch in Japan Signals Strategic Innovation. News, April 21, 2025.