The US Food and Drug Administration has approved the first monoclonal antibody (mAb) to prevent hereditary angioedema (HEA) attacks. Dublin-based Shire was given the go-ahead in August to market Takhzyro (lanadelumab) as prophylactic treatment for HEA types I and II in patients aged 12 years or older. HEA is a rare but life-threatening genetic disease caused by mutations in the C1 esterase inhibitor gene, which leads to an overactivation of the complement system. This can trigger unpredictable bouts of subcutaneous or submucosal swelling anywhere in the body, potentially leading to blocked airways, and in the gut the attacks can cause intense pain, vomiting and dehydration.

Takhzyro is a human mAb against kallikrein, an enzyme that is elevated in the disease and is known to interact with the complement system. The drug's approval was based on data from four clinical studies, including a 26-week phase 3 trial in 125 patients. They experienced 87% fewer HEA attacks if injected every 2 weeks and 73% fewer if injected every 4 weeks, compared with placebo.

Takhzyro entered Shire's portfolio of HEA therapies when the company acquired Dyax of Burlington, Massachusetts, in 2016 (Nat. Biotechnol. 34, 7, 2016). Shire also owns a portfolio of drugs for treating or preventing HEA attacks, including Firazyr (icatibant), a bradykinin B2 receptor, and Kalbitor (ecallantide), a kallikrein inhibitor. These drugs are self-administered subcutaneously, as is Takhzyro. The latter requires fewer injections than the other approved drugs, which are also more limited in their efficacy and carry more health risks. (Kalbitor is not approved in Europe owing to concerns about anaphylactic events.) These drugs also include attenuated androgens, fibrinolytic agents, and intravenous human or recombinant C1 esterase inhibitors—such as Shire's own Cinryze, CSL Behring's Berinert and Pharming Group's Ruconest.

An oral alternative is also in development. A once-daily selective inhibitor of kallikrein developed by BioCryst Pharmaceuticals is being tested in two phase 3 trials for HAE prevention and in a phase 2 trial for treating acute HAE attacks. If approved, the small molecule BCX7353 could become the first oral—and easiest-to-use—therapy for both HEA treatment and prevention.