Takhzyro (lanadelumab) is an approved under-the-skin injection to prevent angioedema attacks in people with type 1 and 2 hereditary angioedema (HAE), ages 12 and older.

Dyax initially developed the treatment. Shire, which is now part of Takeda, later acquired Dyax.

How does Takhzyro work?

HAE is characterized by sudden, unpredictable attacks of non-itchy swellings under the skin. 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.

These swellings also can sometimes occur in the mucous membranes of the lungs or intestinal tract.

Takhzyro is a human monoclonal antibody, or a protein that binds to and inactivates another protein. It targets kallikrein in the body’s circulation, stopping its action and lowering levels of bradykinin.

Takhzyro in clinical trials

A Phase 1 clinical trial (NCT01923207), completed in 2014, 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 total of 38 patients with type 1 or 2 HAE were tested with the treatment in a Phase 1b trial (NCT02093923) that concluded in 2015. 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 the 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 results appeared 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. Among the 32 participants, 16 were Japanese and the other 16 were non-Hispanic Caucasians. This study ended in May 2018, and the results are available on the clinical trials website. None of the participants reported any serious adverse events.

HELP, a Phase 3 clinical trial (NCT02586805), 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.

Results from this trial, which ended in April 2017, 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 such symptoms.

An additional analysis of the data, published by researchers in the journal Allergy, showed that Takhzyro significantly decreases the number of attacks in HAE patients. The treatment started to make a noticeable difference within two weeks of the therapy’s start, the results also showed.

An open-label extension of the HELP trial (NCT02741596) continued to observe patients treated with Takhzyro, at 300 mg every two weeks, for another year and two months, to confirm its long-term safety and treatment benefits. The study also recruited patients who had not taken part in the HELP trial (212 in total). It concluded in October 2019.

Results were presented at the 2020 American College of Allergy, Asthma, and Immunology (ACAAI) Virtual Annual Scientific Meeting and were published in the journal Annals of Allergy, Asthma & Immunology. Compared with the start of the trial, patients had an 87.4% decrease in the average number of HAE attacks. Almost half (47.8%) of the patients in the study went at least nine months without an attack after initially starting treatment. A large percentage (81.8%) had at least a six-month period without attacks while 68.9% of patients had at least a year without an attack.

Ongoing clinical trials

A Phase 3 open-label safety study, called SPRING, (NCT04070326) now is investigating Takhzyro in young children, ages 2 to 11, with HAE. Those enrolled receive treatment with Takhzyro at 150 mg every two weeks for 52 weeks (one year), with a four-week follow-up period. The trial enrolled 20 children at locations in the U.S., Canada, Germany, Hungary, and Spain. In addition to safety, researchers will assess the treatment’s pharmacokinetics and pharmacodynamics. The trial is due to conclude in December 2021.

Another Phase 3 trial (NCT04180163), which is recruiting, 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 (one year), with a four-week follow-up period. Treatment will be given at 300 mg every two weeks for 26 weeks (six months), and then the same dose every two or four weeks for another 26 weeks. The study is enrolling at multiple sites in Japan and will conclude in December 2021.

Two prospective observational studies, evaluating Takhzyro’s effectiveness in real-life use, also are 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 for 36 months (three years) and record the number of HAE attacks. ENABLE is due to end in April 2024, while EMPOWER will conclude in September 2023.

Other information

The U.S. Food and Drug Administration approved Takhzyro in August 2018 to treat patients, ages 12 and older, with types 1 and 2 HAE, at a recommended dose of 300 mg every two weeks. The European Commission (EC) approved it in December 2018 for the routine prevention of HAE attacks in patients ages 12 and older.

The treatment also is approved as a preventive treatment for HAE attacks in Canada, Australia, and China.

 

Last updated: Jan. 4, 2021

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