A marketing authorization application for Lanadelumab, Shire‘s investigational therapy for hereditary angioedema (HAE), was recently cleared by the Swiss Agency for Therapeutic Products (Swissmedic), the company announced.
Supported by data from four clinical trials, acceptance of the marketing authorization application signals that the formal review process of the therapy can now begin. Swissmedic also gave the treatment orphan drug status. It was previously granted priority review in the United States, Europe, Canada and Australia.
HAE is a rare disease that causes debilitating and sometimes life-threatening swelling in the body. These edema attacks can affect several parts of the body, and on average, patients must take 20 days away from work or school per year to deal with the attacks.
Lanadelumab is an investigational monoclonal antibody designed to bind to and inhibit plasma kallikrein. High levels of this protein are the underlying cause of HAE. It is being evaluated for the prevention of angioedema attacks in patients 12 years and older.
“Today’s announcement represents another important step forward as we continue our work to make lanadelumab available to the global HAE community. For those living with HAE, the recurring attacks of swelling can be debilitating,” Andreas Busch, PhD, executive vice president and head of research and development at Shire, said in a press release. “Lanadelumab, if approved, has the potential to change the HAE treatment landscape by directly targeting plasma kallikrein to inhibit excessive bradykinin formation, which stops the blood vessel permeability that causes these swelling attacks.”
Lanadelumab’s regulatory pathway has been determined by the results of several trials that tested the medication’s safety, effectiveness, and tolerability in HAE patients.
In a Phase 1 clinical trial (NCT01923207), single doses of lanadelumab were shown to be safe and well-tolerated in healthy volunteers, with headaches being the most common side effect reported.
In another Phase 1b trial (NCT02093923) the medication was tested in 38 HAE patients. Researchers found that two 300 mg injections of lanadelumab ended patients’ attacks. Those who had two 400 mg injections saw their attacks drop by 88 percent.
Another Phase 1 trial (NCT03401671) is evaluating a single 300 mg injection of lanadelumab under the skin to study the medicine’s pharmacokinetics (how the body processes a medication), pharmacodynamics (how the medication affects the body), safety, and tolerability. The trial is scheduled to end in June 2018.
An important study for lanadelumab’s regulatory approvals was the Phase 3 HELP trial (NCT02586805), which covered patients ages 12 and older with type 1 or 2 HAE. The trial showed that 300 mg injections every two weeks led to an 87% decrease in HAE attacks. The study treated patients with 300 mg of lanadelumab under the skin every two weeks or every month, 150 mg every month, or placebo. All patients were observed for six months. The most common side effect was pain at the injection site, which was experienced by 43% of those on the medication and 30% of those on the placebo.
The Phase 3 HELP trial ended in April 2017. An extension of the trial (NCT02741596) is continuing to observe these patients on the same doses of medication for another year and two months, to confirm the long-term safety and benefits of lanadelumab.
The extension study is being conducted in the U.S, Canada, Germany, Israel, Italy, Puerto Rico, and the U.K. and is scheduled to end in November 2019.