FDA approves Andembry as preventive treatment for HAE
Therapy is only one to target clotting protein FXIIa, implicated in swelling
The U.S. Food and Drug Administration (FDA) has approved Andembry (garadacimab-gxii) to prevent swelling attacks caused by hereditary angioedema (HAE) in adults and adolescents, ages 12 and older, adding the U.S. to the countries where the medication is available.
Developed by CSL Behring, it’s the only treatment for HAE that targets activated factor XII (FXIIa), a clotting protein that triggers a cascade that leads to swelling. It’s also the only treatment given once monthly as an injection under the skin, or subcutaneously, using a prefilled autoinjector that can be self-administered in 15 seconds or less.
“Andembry, a novel once-monthly subcutaneous treatment that inhibits factor XIIa, is a welcome addition to the HAE treatment landscape,” Anthony J. Castaldo, CEO and chairman of the board at the U.S. HAE Association, said in a CSL press release.
The company expects to launch Andembry in the U.S. very soon.
The U.S. approval arrives more than a year after the FDA agreed to review the company’s biologics license application requesting the therapy’s approval, and a few months after Andembry was approved for the same indication in Australia and the U.K., the European Union, Switzerland, and Japan.
Castaldo, who also serves as chairman of the board at HAE International, said HAE patients “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.”
In HAE and other types of angioedema, fluid leaks from small blood vessels and builds up under the skin or in mucous membranes, leading to swelling in the surrounding tissues. When it’s activated, FXII triggers chemical events that lead to swelling attacks.
How does Andembry work in HAE?
Garadacimab, the active ingredient in Andembry, is a monoclonal antibody that inhibits FXIIa. Unlike other medications that act further downstream in the cascade of events leading to swelling, Andembry targets the top of the cascade to stop those initial chemical events from even occurring.
Andembry is available in single doses as a prefilled autoinjector or a syringe with needle. Following an initial loading dose of 400 mg — divided into two 200 mg injections — the therapy is administered once monthly at a maintenance dose of 200 mg. Injections may be self-administered or given by a caregiver.
“Andembry, the first monoclonal antibody discovered and developed entirely by CSL, offers people living with this life-threatening condition long-term control over their disease, along with a convenient administration method,” said Bill Mezzanotte, MD, executive vice president and head of research and development at CSL.
Its approval was backed by data from VANGUARD (NCT04656418), a Phase 3 clinical study where nearly two-thirds (62%) of HAE patients treated with Andembry remained free from swelling attacks over six months. None of the patients assigned to a placebo remained free from attacks. The study included 64 adults and teens with HAE types 1 or 2, ages 12 and older, who’d had at least three attacks in the three months ahead of screening.
During the study, those taking Andembry had a mean of 0.27 swelling attacks a month, while those on a placebo had about two. After taking the frequency of previous attacks into account, this corresponded to a 89.2% reduction in attack frequency over a placebo. Patients on Andembry also had fewer swelling attacks that required on-demand treatment and fewer moderate or severe attacks than those on a placebo.
“Many patients still experience painful and sometimes life-threatening HAE attacks and require frequent injections,” said Tim Craig, a professor at Penn State University who led VANGUARD. “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 most common side effects with Andembry in VANGUARD and its ongoing open-label extension (NCT04739059) include injection site reactions such as bruising, skin reddening, pruritus (itching), and rash, as well as abdominal pain and cold-like symptoms.
According to an interim analysis from the open-label extension, Andembry appears to be safe for long-term use as a preventive treatment and continues to reduce the frequency of swelling attacks in people with HAE after more than a year.
Healthcare professionals and patients can learn more or get support through Andembry Connect.
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