The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending the granting of marketing authorisation of Lanadelumab injection for routine prevention of recurrent attacks of HAE in patients aged 12 years and older. If approved, Lanadelumab will be a first-of-its-kind, fully human monoclonal antibody (mAb) available in the EU that inhibits the activity of plasma kallikrein, an enzyme which is uncontrolled in people with HAE, to help prevent attacks.
“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,” said Andreas Busch, Ph.D., Executive Vice President, Head of Research and Development at Shire plc. “We are excited about the future potential of Lanadelumab in helping to address the needs of those living with this chronic and unpredictable disease.”
The positive opinion is supported by data from the Phase III HELP (Hereditary Angioedema Long-term Prophylaxis) Study, the largest randomized controlled prevention study conducted to date in HAE, which evaluated the efficacy and safety of subcutaneously administered Lanadelumab versus placebo over 26 weeks in 125 patients 12 years of age or older with HAE.
Lanadelumab was previously granted accelerated assessment by the EMA, reducing the number of evaluation days required from 210 to 150. The CHMP’s positive opinion will be reviewed by the European Commission, which has the authority to grant marketing authorization in the EU.
Lanadelumab received approval for the prevention of HAE attacks in patient 12 years and older in the U.S. on 23 August 2018 and Canada on 19 September 2018, under the brand name TAKHZYRO.
The primary endpoint of the HELP Study was the number of investigator-confirmed HAE attacks over the entire 26-week study duration. Lanadelumab demonstrated that subcutaneous injections every two or four weeks reduced the mean monthly number of attacks across all three Lanadelumab treatment arms studied: 300 mg every two weeks, 300 mg every four weeks, and 150 mg of Lanadelumab every four weeks. At 300 mg every two weeks, Lanadelumab reduced the number of mean monthly HAE attacks by 87% vs. placebo (adjusted P<0.001).
Overall, each Lanadelumab treatment arm demonstrated statistically significant attack rate reductions compared with placebo for all secondary efficacy endpoints (adjusted P<0.001 for all comparisons). Patients taking Lanadelumab 300 mg every 2 weeks had 83% fewer moderate or severe attacks and 87% fewer attacks that needed on-demand treatment. A pre-specified, exploratory analysis showed that 44% of patients (n=27) receiving Lanadelumab 300 mg every two weeks had zero attacks compared to placebo (2%, n=41) for the 26-week treatment period. Additionally, in a post hoc sensitivity analysis of the steady state period from Day 70 to Day 182, 77% of patients (n=26) treated with Lanadelumab in the same dosage arm of the trial were attack-free compared to placebo (3%, n=37).