European regulators approve garadacimab as Andembry for HAE
Treatment is designed to halt bradykinin production, prevent swelling attacks
The European Commission has approved Andembry (garadacimab) as a monthly treatment for preventing swelling attacks in people with hereditary angioedema (HAE), ages 12 and older.
The decision, which is consistent with a recommendation issued by a European Medicines Agency committee last year, is valid in all countries of the European Union, as well as Iceland, Liechtenstein, and Norway. Developer CSL indicated Andembry will be made available to eligible patients in these areas after access and reimbursement negotiations have been completed.
Andembry, which is self-administered under the skin, or subcutaneously, once a month via a prefilled injection pen, was also approved by regulators in Australia and the U.K. last month. Decisions are pending in the U.S., Japan, Switzerland, and Canada.
“Andembry is a significant advancement in the management of hereditary angioedema, offering people living with this life-threatening condition long-term control over their disease with a patient-centric, convenient administration method,” Bill Mezzanotte, MD, CSL’s executive vice president and head of research and development, said in a company press release. “Thank you to all the colleagues, physicians and patients who contributed to this exciting milestone.”
In HAE, genetic mutations lead to the overproduction of the signaling molecule bradykinin, which drives the swelling episodes that characterize the disease. Swelling can happen anywhere on the body and at any time.
“The unpredictable nature of HAE is one of the most daunting aspects for many patients, who never know when an attack might occur,” said Markus Magerl, MD, head of clinical trials at Charité University Hospital Berlin’s Institute of Allergology in Germany.
Studies support Andembry’s approval
Garadacimab, the active ingredient in Andembry, is an antibody that’s designed to halt the chain of events that lead to bradykinin production to prevent swelling attacks. It blocks factor XII (FXII), the activated form of the protein responsible for kickstarting the process. Activated FXII is what normally prompts the formation of the enzyme kallikrein, which is needed to produce bradykinin.
“Current HAE preventive therapies work at various downstream steps in the cascade, but none prevent the cascade at its very start like Andembry,” Magerl said.
Andembry’s regulatory approvals are supported by data from the six-month, placebo-controlled Phase 3 VANGUARD trial (NCT04656418) and an ongoing open-label extension study (NCT04739059), both involving HAE patients, ages 12 and older.
In VANGUARD, Andembry was associated with a more than 85% reduction in the mean rate of monthly swelling attacks relative to a placebo, with two-thirds of treated patients being completely free from attacks. That didn’t happen for anyone on the placebo. Data from the extension study, where VANGUARD participants and other HAE patients are all receiving Andembry, has likewise indicated it can safely prevent swelling attacks in the long term.
The most commonly observed side effects associated with Andembry are injection site reactions, such as redness, bruising, and itching.
“[Andembry] … is a welcome addition to the HAE treatment landscape,” said Henrik Balle Boysen, president of HAE International. “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.”
CSL is also sponsoring a Phase 3 trial (NCT05819775) to test Andembry in children with HAE, ages 2-11. The study is expected to finish next year.
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