The Journal of the American Medical Association (JAMA) publishes the complete results from the Phase 3 HELP Study™, a randomised, placebo-controlled trial evaluating the efficacy and safety of subcutaneously administered Lanadelumab versus placebo over 26 weeks in 125 patients 12 years of age or older with HAE. The HELP Study™ is the largest randomised controlled prevention study ever conducted to date in HAE.
Lanadelumab, which is approved under the brand name TAKHZYRO™ in the U.S. and Canada, is a first-of-its-kind monoclonal antibody that inhibits the activity of plasma kallikrein, an enzyme which is uncontrolled in people with HAE, to help prevent attacks.
The study met all primary and secondary endpoints, with all three Lanadelumab treatment regimens demonstrating statistically significant reductions in the mean monthly HAE attack rate compared to placebo. At 300 mg every two weeks, Lanadelumab reduced the number of mean monthly HAE attacks by 87% relative to placebo (adjusted P<0.001). Patients receiving Lanadelumab 300 mg every two weeks had 83% fewer moderate to severe attacks (vs. placebo), 87% fewer attacks that needed on-demand treatment (vs. placebo) and an 89% attack rate reduction (vs. placebo) from day 14 to 182.
“HAE can be an unpredictable disease which requires an individualised approach to treatment,” said Aleena Banerji, MD, Massachusetts General Hospital, Boston, Mass. and principal investigator of the clinical trial. “The findings from HELP support the use of Lanadelumab as a subcutaneous prophylactic therapy to prevent HAE attacks in appropriate patients, helping address the need for new treatment options.”
A pre-specified, exploratory analysis showed that over the entire 26-week study period, 44% of patients receiving Lanadelumab 300 mg every two weeks (n=12/27) were attack-free vs. 2% of patients receiving placebo (n=1/41). Additionally, in a post-hoc sensitivity analysis of the steady-state period of the last 16 weeks of the study, 77% of patients (n=20/26) receiving Lanadelumab 300 mg every two weeks were attack-free vs. 3% of patients on placebo (n=1/37).
“We are excited about the potential of Lanadelumab.” said Donatello Crocetta, Head, Global Medical Affairs, Immunology at Shire plc. “Data from HELP demonstrate the efficacy of Lanadelumab in preventing HAE attacks over the entire duration of the study, with many patients remaining attack-free during the 16-week steady state period. We remain focused on our work to help make Lanadelumab available to patients living with HAE in additional countries around the world.”
A clinically meaningful improvement was also observed in 81% of patients treated with Lanadelumab 300 mg every two weeks based on the Angioedema Quality of Life Questionnaire (AE-QoL) compared to 37% of patients in the placebo group. The AE-QoL measures the impact of angioedema over a four-week period across four domains: fear/shame, functioning, fatigue/mood, and nutrition.
The most commonly reported treatment-emergent adverse events (excluding HAE attacks) in patients treated with Lanadelumab during the entire treatment period were injection site pain (42.9%), viral upper respiratory tract infection (23.8%), headache (20.2%), injection site erythema (9.5%), injection site bruising (7.1%), and dizziness (6.0%). Most treatment-emergent adverse events (98.5%) were mild to moderate in severity. The most commonly reported treatment-emergent adverse events in patients treated with Lanadelumab that were considered related to treatment were injection site pain (41.7%), injection site erythema (9.5%), injection site bruising (6.0%), and headache (7.1%). There were no deaths or related serious treatment-emergent adverse events.