How lanadelumab works
Hereditary angioedema, or HAE, is a condition that involves sudden, unpredictable attacks of non-itchy swelling under the skin or in the mucous membranes of the lungs or intestinal tract.
The swelling is caused by excessive amounts of bradykinin, an inflammatory substance that causes blood vessels to become leakier. The amount of bradykinin released is tightly controlled by another molecule called kallikrein.
Lanadelumab is a human monoclonal antibody, or a protein that binds to and inactivates another protein. It targets kallikrein in blood circulation, stopping its action and reducing bradykinin. It is being developed as a preventive treatment for HAE attacks.
Lanadelumab in clinical trials
A Phase 1 clinical trial (NCT01923207) showed that single doses of lanadelumab of up to 3 mg/kg were safe and well tolerated in healthy volunteers. Headaches were the most common side effect, experienced by a quarter of the patients in both the medication and placebo groups. The results of the study were published in the Annals of Allergy, Asthma & Immunology.
Researchers conducted a Phase 1b trial (NCT02093923) that tested the medication in 38 patients. The group had either type 1 or 2 HAE. They 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 lanadelumab ended patients’ attacks. Those who had two 400-mg injections saw their attacks drop by 88 percent. In both groups, the doses were given two weeks apart. All patients were monitored for four months. The trial ended in 2015, with the results published in the New England Journal of Medicine.
Another Phase 1 trial (NCT03401671) is investigating a single 300-mg injection of lanadelumab under the skin. Researchers are looking at the injection’s pharmacokinetics (how the body processes a medication), pharmacodynamics (how the medication affects the body), safety, and tolerability. The trial is ongoing but no longer recruiting participants. It is scheduled to end in June 2018.
The Phase 3 HELP trial (NCT02586805) covered patients ages 12 and older with type 1 or 2 HAE. It showed that 300-mg injections every two weeks led to patients experiencing 87 percent fewer attacks. During the study, patients received 300 mg of lanadelumab under the skin every two weeks or every month, 150 mg every month, or a placebo. They were observed for six months. The most common side effect was pain at the injection site, felt by 43 percent of those on the medication and 30 percent of those on the placebo. The trial ended in April 2017.
An extension of the HELP trial (NCT02741596) is continuing to observe these patients on the same doses of medication for another year and two months. The extension aims to confirm the long-term safety and benefits of lanadelumab. It is occurring at sites in the U.S, Canada, Germany, Israel, Italy, Puerto Rico, and the U.K. It is scheduled to end in November 2019.
Lanadelumab has been given orphan drug status by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). This designation grants companies certain exemptions and rights in developing therapies that could benefit patients with rare diseases. Lanadelumab has also been awarded breakthrough therapy designation, meant to speed up the development and regulatory review of new compounds.
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