FDA Approves Hereditary Angioedema Therapy, Andembry

The FDA has approved CSL Behring’s Andembry (garadacimab-gxii), a new therapy for the prophylactic treatment of hereditary angioedema (HAE) in patients aged 12 years and older, according to a news release. Andembry is now the first and only treatment targeting factor XIIa, a key initiator of the biological cascade that causes swelling attacks in people with HAE.

Hereditary angioedema is a rare, chronic and potentially life-threatening genetic condition affecting approximately 1 in 50,000 people. It is caused by deficient or dysfunctional C1 inhibitor protein, leading to spontaneous episodes of swelling that may affect the abdomen, face, throat or extremities. If untreated, HAE attacks—especially those impacting the airway—can result in suffocation and death.

Andembry is a monoclonal antibody designed to block the activated form of the plasma protein factor XII (FXIIa), preventing the onset of swelling episodes at the very top of the HAE cascade. Unlike existing therapies, which typically target downstream mediators or require more frequent administration, Andembry is a once-monthly subcutaneous injection delivered in under 15 seconds via an autoinjector with a citrate-free formula.

The drug’s approval is based on the results of the phase 3 VANGUARD trial, a randomized, double-blind study that demonstrated Andembry’s efficacy.

• 62% of patients on Andembry experienced no attacks during the treatment period.
• Median attack reduction was more than 99%, and least squares mean reduction was 89% compared to placebo.
• It also reduced the number of attacks requiring on-demand therapy by approximately 88% and reduced the number of moderate or severe attacks by approximately 90%, compared to placebo.

The recommended dose of Andembry is a 400 mg loading dose, followed by a monthly 200 mg maintenance dose, according to the prescribing information.

In terms of safety, the most common side effects observed were nasopharyngitis and abdominal pain, both observed in at least 7% of patients. An interim analysis from an ongoing open-label extension study has reinforced these findings, showing that Andembry maintains a favorable safety profile with sustained efficacy over time. Injection-site reactions such as pruritus, urticaria, and hematoma were reported in approximately 14% of participants.

Andembry marks a milestone for CSL as the company’s first discovered and developed recombinant monoclonal antibody to gain FDA approval.

Medical experts and advocacy groups welcomed the approval.

"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," Tim Craig, DO, professor of medicine, pediatrics and biomedical sciences at Penn State University, said in the news release. "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."

"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," Anthony J. Castaldo, CEO and chairman of the board of the U.S. HAE Association and HAE International, said in the news release.

CSL Behring will begin commercial launch in the United States immediately, with availability expected by the end of June 2025.