Garadacimab approved to prevent HAE attacks in UK, Australia
Available there as Andembry, regulatory decisions awaited in US and EU

CSL’s garadacimab, under the brand name Andembry, has been approved in the U.K. and Australia for the routine prevention of swelling attacks in adults and adolescents with hereditary angioedema (HAE), ages 12 and older.
In Australia, the therapy is intended for HAE patients with deficiency or dysfunction of the C1-esterase inhibitor (C1-INH) protein, which is the cause of HAE types 1 and 2. It is not yet known if U.K. regulators are making a similar distinction, but this was the patient group in the pivotal clinical trial whose findings support requests for the treatment’s approval.
These two clearances are the first for the injectable therapy, which is under review in the U.S., Japan, Switzerland, Canada, and the European Union (EU). In the EU, a committee recently issued a positive opinion recommending the therapy’s approval for patients ages 12 and older.
“Today’s news represents a significant milestone for people living with hereditary angioedema,” Paul McKenzie, CEO and managing director of CSL, said in a company press release. “We look forward to making this medicine accessible to patients in the future, to address unmet needs in the HAE community.”
Garadacimab, an antibody, blocks events that lead to swelling
HAE is due to genetic mutations that lead to the overproduction of bradykinin, a signaling molecule that drives swelling in the deep layers of the skin or mucus membranes lining internal organs and body cavities. Swelling episodes that can occur anywhere on the body affect patients.
Bradykinin production relies on an enzyme called kallikrein, which is formed when the blood clotting protein factor XII (FXII) is activated. Garadacimab is an antibody designed to block the activated form of FXII, ultimately halting the chain of events that leads to bradykinin and swelling.
The treatment is given via monthly under-the-skin (subcutaneous) injections, which can be self-administered using a prefilled injector pen. After an initial loading dose of 400 mg spread over two injections, it’s given as a single 200 mg injection each month.
Bill Mezzanotte, MD, CSL’s executive vice president and head of research and development, noted that Andembry was “homegrown,” initially developed by company scientists at laboratories in Melbourne, Australia, the company’s home country.
More than 500 people in Australia are estimated to be living with the rare swelling disorder. Andembry also has been recommended for funding on Australia’s Pharmaceutical Benefits Scheme, a government program that subsidizes the cost of medications for residents and other eligible individuals.
“The regulatory approval of a new treatment option is an important step towards improving health outcomes of Australians living with this condition,” said Constance Katelaris, PhD, a professor of immunology and allergy at Campbelltown Hospital in New South Wales.
Treated patients in Phase 3 trial had 85% drop in monthly swelling attack rate
In both Australia and the U.K., Andembry’s approval came through the ACCESS pathway, a consortium of regulatory authorities working together to align on regulatory requirements for investigational treatments.
“Patient safety is our top priority,” Julian Beach, executive director of healthcare quality and access for the U.K.’s Medicines and Healthcare products Regulatory Agency, said in a separate press release. “We’re assured that the appropriate regulatory standards of safety, quality and efficacy for the approval of this new medicine have been met.”
Regulatory applications for Andembry were supported by efficacy and safety data from the Phase 3 VANGUARD trial (NCT04656418) and its ongoing open-label extension study (NCT04739059).
VANGUARD tested Andembry against a placebo in 64 HAE patients, ages 12 and older, who had at least three swelling attacks in the three months before entering the trial.
Andembry-treated patients had a more than 85% reduction in the mean rate of monthly swelling attacks relative to those on a placebo. Nearly two-thirds of these people also were free of swelling attacks across the six-month study, while no placebo-group patients were.
In the open-label extension, evaluating the treatment’s long-term safety and efficacy, VANGUARD participants and other HAE patients are receiving monthly injections of Andembry. Interim data indicate the treatment is safe and leading to sustained attack prevention.
The most common side effects associated with Andembry are injection site reactions, such as swelling, bruising, and itching that is usually mild and resolves within a few days. Other adverse events observed in treated patients in clinical trials include upper respiratory tract infection, cold-like symptoms, and headache.