UK MHRA Approves Garadacimab for Preventing Angioedema Attacks

Artur - stock.adobe.com

The UK Medicines and Healthcare products Regulatory Agency (MHRA) announced on Jan. 24, 2025 that it has approved Australia-based CSL Behring’s garadacimab (brand name ANDEMBRY) to prevent angioedema attacks in patients 12 years old and older who have hereditary angioedema (HAE). The approval was granted through an Access Consortium work-sharing procedure, according to the agency’s press release (1). The Access Consortium is a medium-sized coalition of regulatory authorities that work to promote greater regulatory collaboration and to align regulatory requirements worldwide (2).

A biologic, garadacimab is administered by injection subcutaneously. Garadacimab is a recombinant monoclonal antibody that targets activated Factor XII (FXII), a coagulation protein (3). When activated, FXII becomes FXIIa, the latter of which initiates the kallikrein-kinin cascade of HAE attacks. Garadacimab inhibits this cascade by targeting FXIIa at the top of the cascade reaction. In comparison, other HAE therapies target downstream mediators in this cascade (1).

“Patient safety is our top priority, which is why I am pleased to confirm approval of garadacimab for patients with hereditary angioedema to prevent angioedema attacks,” said Julian Beach, MHRA interim executive director of Healthcare Quality and Access, in the agency press release (1). “We’re assured that the appropriate regulatory standards of safety, quality, and efficacy for the approval of this new medicine have been met. As with all products, we will keep its safety under close review.”

HAE is a rare condition that causes fluid buildup throughout the body. The buildup of fluid triggers sudden and repeated serious swelling. Because it is hereditary, HAE often runs in families, but some people may not have a family history, according to the press release.

A study was done using 64 adult and pediatric patients with HAE who have experienced at least two attacks during the run-in period, which lasted up to two months.

“The study showed that [with] over six months of treatment, patients taking garadacimab had a lower monthly rate of HAE attacks compared with patients given placebo. Additionally, more patients taking garadacimab were attack-free during the first three months of treatment compared to placebo,” MHRA stated in its press release.

CSL Behring’s biologics license application and marketing authorization application (MAA) for garadacimab was accepted by FDA and the European Medicines Agency (EMA), respectively, in December 2023 (4). A year later in December 2024, EMA’s Committee for Medicinal Products for Human Use gave a positive opinion on the MAA and recommended approving the application (5).

In the most recent regulatory filing update, the Australian Therapeutic Goods Administration approved the registration of garadacimab on Jan. 24, 2025 for the routine prevention of recurrent HAE attacks in patients 12 years old and older with C1-esterase inhibitor deficiency or dysfunction (6).

“As an Australian company with a global footprint, we take great pride that [garadacimab] is our first monoclonal antibody treatment and was discovered in our labs in Australia. We look forward to making this medicine accessible to patients in the future, to address unmet needs in the HAE community,” said Paul McKenzie, chief executive officer and managing director, CSL, in a company press release (6).

In addition to Europe, the US, the UK, and Australia, the product is also under review by regulatory agencies in Japan, Switzerland, and Canada.

References

1. Medicines and Healthcare products Regulatory Agency. Garadacimab (Andembry) Approved to Prevent Angioedema Attacks. Press Release. Jan. 24, 2025.
2. Government of the United Kingdom. Access Consortium. www.gov.uk (accessed Jan. 30, 2025).
3. Stavrou, E.; Schmaier, A. H. Factor XII: What Does It Contribute to Our Understanding of the Physiology and Pathophysiology of Hemostasis & Thrombosis. Thromb. Res. 2010, 125 (3), 210–215. DOI: 10.1016/j.thromres.2009.11.028
4. CSL Behring. CSL's Garadacimab, a First-in-Class Factor XIIa Inhibitor, Receives FDA and EMA Filing Acceptance. Press Release. Dec. 14, 2023.
5. CSL Behring. CSL Receives Positive CHMP Opinion for Garadacimab in Hereditary Angioedema (HAE). Press Release. Dec. 13, 2024.
6. CSL Behring. Australia’s Therapeutic Goods Administration (TGA) Approves Registration of CSL’s ANDEMBRY (garadacimab) for the Prevention of Recurrent Hereditary Angioedema (HAE) Attacks. Press Release. Jan. 24, 2025.