CSL’s Andembry (Garadacimab) Gets FDA Approval as New HAE Prophylactic Option

The FDA has approved CSL’s Andembry (garadacimab-gxii), a first-of-its-kind prophylactic treatment for hereditary angioedema (HAE) that targets factor XIIa (FXIIa).

Unlike other therapies, Andembry is approved for once-monthly subcutaneous dosing from the outset for all patients aged 12 and older.

What Is HAE?

HAE is a rare and potentially life-threatening condition that causes unpredictable attacks of swelling in areas such as the face, abdomen and throat. The condition affects an estimated 1 in 10,000 to 1 in 50,000 people globally.

HAE attacks are triggered by a deficiency or dysfunction of the C1 inhibitor protein, which typically regulates the inflammatory response. When this regulatory control breaks down, bradykinin — a peptide that increases blood vessel permeability — builds up in the body. The result: fluid leaks into nearby tissues, causing swelling that can be painful, interfere with daily activities and in rare cases involving the throat, become life-threatening.

An Orphanet review, which analyzed data from over 10,000 patients, estimated an 8.6% risk of death from untreated laryngeal swelling due to asphyxiation. On average, individuals affected by this severe form of HAE died nearly three decades earlier than those with other causes of death.

A recent Harris Poll commissioned by Ionis Pharmaceuticals also suggested a persistent gap between disease control and patient satisfaction. The poll found that 91% of surveyed US adults with HAE expressed interest in trying new therapies, with 65% reporting they still haven’t found the best treatment option. Nearly 70% reported living in fear of unpredictable attacks, and 89% said they avoided or missed important activities — from work to travel — due to HAE. Fewer than half of patients said they shared all symptoms with their doctors, and only 36% reported using a standardized tool like the Angioedema Control Test.

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Andembry Shows Sustained HAE Attack Reduction in Phase III

Andembry works by targeting activated FXIIa, the initiator of the biochemical cascade that leads to HAE attacks. By inhibiting FXIIa at the top of the pathway, it prevents the chain reaction from triggering bradykinin production. The once-monthly autoinjector formulation takes less than 15 seconds to administer and does not require titration.

The approval is based on data from the Phase III VANGUARD trial. In this placebo-controlled study, garadacimab reduced HAE attacks by more than 99% in the middle range of patients and by an average of 89.2% across the full study group, compared to placebo.

Additionally, 62% of patients receiving Andembry remained attack-free during the six-month treatment period. The trial also showed over 99% median reduction in both attacks requiring on-demand therapy and those classified as moderate or severe.

The most common side effects in the trial (occurring in ≥7% of participants) were nasopharyngitis and abdominal pain. Injection-site reactions such as redness and bruising were reported in 14% of patients.

A 2024 interim analysis from an open-label extension trial published in Allergy supported a favorable safety profile over 14 months of median exposure.

Next Steps and Other HAE Drug Candidates

The new approval is part of CSL’s long-standing involvement in HAE, with Andembry representing its first monoclonal antibody developed entirely in-house and adding to a strategic expansion of its four-decade-long HAE portfolio.

The company plans to make the treatment commercially available in the US by the end of June 2025 and has already secured approvals in the European Union (EU), UK, Japan, Australia and other regions.

Andembry joins the approved Orladeyo (berotralstat) from BioCryst Pharma, along with investigational treatments like KalVista’s sebetralstat, which is currently facing FDA review delays due to agency resource constraints. Astria Therapeutics’ investigational navenibart also remains in development, having recently demonstrated sustained attack rate reductions in the long-term ALPHA-SOLAR trial presented at the European Academy of Allergy and Clinical Immunology (EAACI) 2025.

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