How does Takhzyro work?
HAE is characterized by sudden, unpredictable attacks of non-itchy swellings under the skin. These swellings can also sometimes occur in the mucous membranes of the lungs or intestinal tract. They are caused by excessive amounts of bradykinin, an inflammatory substance that causes the blood vessels to become leaky. Another molecule called kallikrein tightly controls the amount of bradykinin released into the bloodstream.
Takhzyro is a human monoclonal antibody or a protein that binds to and inactivates another protein. It targets kallikrein in the circulation, stopping its action and lowering levels of bradykinin.
Takhzyro in clinical trials
A Phase 1 clinical trial (NCT01923207) showed that single doses of Takhzyro of up to 3 mg per kg were safe and well-tolerated in healthy volunteers. Headaches were the most common side effect, with a quarter of the participants in both the treatment and placebo groups experiencing them.
A Phase 1b trial (NCT02093923) tested the treatment in 38 patients with type 1 or 2 HAE. The patients had experienced attacks at least twice a year, with at least one in the six months before entering the trial. Two 300 mg injections of Takhzyro ended patients’ attacks. Those who had two 400 mg injections saw their attacks drop by 88%. In both groups, patients received doses two weeks apart. Investigators monitored all patients for four months. The trial ended in 2015, with results published in the New England Journal of Medicine.
Another Phase 1 trial (NCT03401671) investigated the pharmacokinetics (movement in the body), pharmacodynamics (effect on the body), safety, and tolerability of a single 300 mg under-the-skin injection of Takhzyro in 32 healthy volunteers. A total of 16 of the participants were Japanese and the other 16 were non-Hispanic Caucasians. This study ended in May 2018. The results are available on the clinical trials website. No participant reported any serious adverse events.
A Phase 3 clinical trial (NCT02586805), called HELP, recruited 125 people, ages 12 and older, with type 1 or 2 HAE to test the safety and efficacy of Takhzyro in preventing acute angioedema attacks. Patients received either 300 mg of Takhzyro injected under the skin every two weeks or every month, 150 mg of Takhzyro every month, or a placebo. Shire reported study results showed that Takhzyro at 300 mg every two weeks led to an 87% mean drop in attack frequency. The most common side effect was pain at the injection site, with 43% of those on the medication and 30% of those in the placebo group experiencing it. The trial ended in April 2017. Raw study results are available on the clinical trials website.
An extension of the HELP trial (NCT02741596) continued to observe these patients, treated with Takhzyro at 300 mg every two weeks, for another year and two months, to confirm the long-term safety and treatment benefits. The study recruited 212 patients and concluded in October 2019. Results have not yet been published.
Ongoing clinical trials
A Phase 3 open-label safety study, called SPRING, (NCT04070326) is investigating Takhzyro in young children with HAE ages 2 to 11. Those enrolled are being treated with Takhzyro at 150 mg every two weeks for 52 weeks and will be followed for another four weeks. The trial is currently enrolling up to 20 children at locations in the U.S., Canada, Germany, Hungary, and Spain. In addition to safety (measured in adverse events) the treatment’s pharmacokinetics and pharmacodynamics will be assessed. The trial is due to conclude in December 2021.
Another Phase 3 trial (NCT04180163) is investigating the safety and efficacy of Takhzyro in eight HAE patients in Japan, ages 12 and older. This trial also runs for 52 weeks, with a four-week follow-up period. Patients will be given the treatment at 300 mg every two weeks for 26 weeks, and then the same dose every two or four weeks for another 26 weeks. The study is also enrolling at multiple sites in Japan and will conclude in December 2021.
Two prospective observational studies, evaluating the Takhzyro’s effectiveness in real-life use, are also enrolling patients. The three-year ENABLE trial (NCT04130191) is recruiting up to 200 people with HAE type 1 or 2 in Austria, Germany, and Switzerland. The three-year EMPOWER trial (NCT03845400) is recruiting 270 participants in the U.S. and Canada. In both studies, investigators will monitor participants who are taking Takhzyro for 36 months and record the number of HAE attacks. ENABLE is due to end in April 2024 and EMPOWER in September 2023.
The U.S. Food and Drug Administration (FDA) approved Takhzyro to treat patients ages 12 and older with types 1 and 2 HAE in August 2018, at a recommended dose of 300 mg every two weeks. The European Commission (EC) approved it for the routine prevention of HAE attacks in patients ages 12 and above in December 2018.
Last updated: March 5, 2020
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