The Committee for Medicinal Products for Human Use (CHMP), an arm of the European Medicines Agency (EMA), favors granting marketing authorization to lanadelumab for routine prevention of hereditary angioedema (HAE) attacks in patients ages 12 and older.
Shire’s lanadelumab is a monoclonal antibody that specifically binds to an enzyme called kallikrein in the blood, decreasing its activity. Kallikrein controls the level of an inflammatory molecule known as bradykinin. If present at higher-than-normal amounts, bradykinin causes swelling in HAE patients.
“This positive opinion marks an important step towards providing adults and adolescents living with HAE in Europe a first-of-its-kind monoclonal antibody treatment option to help prevent attacks,” Andreas Busch, PhD, Shire’s executive vice president, head of research and development, said in a press release.
The European Commission will now review CHMP’s opinion before making a final decision regarding approval. The treatment was recently approved in the U.S. and Canada — under the trade name Takhzyro — for the prevention of HAE attacks in adolescents and adults. In Switzerland, a marketing authorization application was cleared by the Swiss Agency for Therapeutic Products.
“We are excited about the future potential of lanadelumab in helping to address the needs of those living with this chronic and unpredictable disease,” Busch said.
The positive opinion is supported by the findings of the Shire-sponsored HELP Phase 3 trial (NCT02586805), the largest randomized, placebo-controlled prevention study in HAE to date. HELP enrolled 125 patients, ages 12 years or older, with type 1 or type 2 HAE to assess the efficacy and safety of under-the-skin administration of lanadelumab over 26 weeks.
Results of the multicenter, double-blind study showed that lanadelumab reduced the mean number of monthly swelling attacks compared to placebo. This was observed across all three lanadelumab treatment groups: 300 mg every two weeks, 300 mg every four weeks, and 150 mg every four weeks. An average 87% reduction of attacks was found with 300 mg lanadelumab every two weeks, which also improved quality-of-life scores.
HELP also showed that patients on 300 mg lanadelumab every two weeks had 83% less moderate or severe attacks, as well as 87% fewer attacks needing on-demand treatment. Twenty-seven patients (44%) treated with this regimen had zero HAE attacks, compared to only 2% of placebo-treated participants.
Further analysis during the treatment’s steady state period, from day 70 to day 182, demonstrated that 77% of patients receiving 300 mg lanadelumab every two weeks were attack-free compared to 3% of those on placebo.
As a result, the recommended dose of Takhzyro is 300 mg every two weeks, although a four week-interval may be considered if the patient is attack-free for more than six months.
No serious treatment emerging adverse events (TEAEs) or deaths were reported. The most frequent TEAE was HAE attack, with the most common adverse events being injection site pain (42.9%), upper respiratory infection (23.8%), headache (20.2%), and injection site erythema, or skin redness (9.5%).
Most TEAEs were mild to moderate in severity, leading to only one case of treatment discontinuation in the group treated with 300 mg lanadelumab every four weeks (elevation in liver enzymes), and two in those receiving placebo arm (tension headache, HAE attack).