Garadacimab application accepted for FDA review in hereditary angioedema treatment
Click Here to Manage Email Alerts
Key takeaways:
- Garadacimab inhibits the kallikrein-kinin cascade in hereditary angioedema attacks.
- Mean monthly attack rates included 0.27 with treatment and 2.01 with placebo.
- Safety profiles were favorable.
The FDA has accepted a biologics license application for garadacimab as a monthly prophylactic treatment for hereditary angioedema, according to a press release from the manufacturer.
The European Medicines Agency (EMA) also has accepted CSL’s marketing authorization application, the press release said, adding that, if approved, the biologic would become the first treatment for hereditary angioedema (HAE) in the United States and in the European Union that targets activated factor XII (FXIIa).
The FDA and EMA both previously designated garadacimab as an orphan drug for HAE therapy as well.
“We are extremely proud that our first homegrown recombinant monoclonal antibody is progressing our commitment to support HAE patients in need,” Emmanuelle Lecomte-Brisset, PharmD, senior vice president and global head of regulatory affairs at CSL, said in the release.
FXIIa is a plasma protein that initiates the kallikrein-kinin cascade of HAE attacks. Compared with HAE therapies that target downstream mediators, garadacimab (CSL312) inhibits the cascade at its top by targeting FXIIa, according to the release.
Data from the pivotal, multicenter, randomized, double-blind, parallel-group VANGUARD trial supported the biologics license application and the marketing authorization application.
These data indicated that monthly 200 mg doses of garadacimab significantly reduced attack rates among patients aged 12 years and older with type I or II HAE compared with placebo and was well tolerated during a 6-month period.
Patients treated with garadacimab (n = 39) had a mean monthly attack rate of 0.27, and those treated with placebo (n = 25) had a mean monthly attack rate of 2.01 (P < .0001). Median monthly attack rates included 0 for those treated with garadacimab and 1.35 for those treated with placebo.
Also, nearly three-quarters of patients treated with garadacimab were attack-free within the first 3 months of treatment with sustained efficacy through the remainder of the study.
The treatment and placebo groups experienced similar frequencies of treatment-emergent adverse events, most commonly upper respiratory infection, nasopharyngitis and headache among the treatment group, with no bleeding or thrombosis.
VANGUARD is continuing as an ongoing, open-label extension study.
“We believe that garadacimab has the potential to become a promising therapy in the prevention of HAE attacks, and we look forward to working closely with global health regulators throughout the review process,” Lecomte-Brisset said.