Shire plc (LON: SHP, NASDAQ: SHPG), the leading global biotechnology company focused on rare diseases, announced today that the European Commission (EC) has granted Marketing Authorisation for TAKHZYRO™ (lanadelumab) subcutaneous injection, for routine prevention of recurrent attacks of hereditary angioedema (HAE) in patients aged 12 years and older. TAKHZYRO is a first-of-its-kind fully human monoclonal antibody (mAb) that inhibits the activity of plasma kallikrein, an enzyme which is uncontrolled in people with HAE, to help prevent attacks. HAE is a rare, genetic and potentially life-threatening disorder that can result in recurrent attacks of oedema (swelling) in various parts of the body.
Andreas Busch, Ph.D., Executive Vice President, Head of Research and Development at Shire said “We are delighted to receive today’s European approval. For those with HAE, the burden of disease can significantly impact their day to day life, With TAKHZYRO, we can now provide an innovative treatment that has potential to change the way HAE is currently treated.”
The recommended starting dose is 300 mg lanadelumab every two weeks. In patients who are stably attack free on treatment, a dose reduction of 300 mg lanadelumab every four weeks may be considered, especially in patients with low weight.
The Phase III HELP (Hereditary Angioedema Long-term Prophylaxis) Study™ supporting the approval was recently published in JAMA. The primary endpoint was the number of investigator-confirmed HAE attacks over the entire 26-week study duration. TAKHZYRO reduced the mean number of monthly HAE attacks by 87% relative to placebo when administered at 300 mg every two weeks and 73% relative to placebo when administered at 300 mg every four weeks (adjusted P<0.001).
Overall, each TAKHZYRO 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 TAKHZYRO 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. A prespecified, exploratory analysis showed that over the entire 26-week study (Days 0-182), 44% (n=12/27) of patients taking TAKHZYRO 300 mg every two weeks were attack-free vs. 2% (n=1/41) of patients taking placebo. Additionally, it is anticipated that TAKHZYRO reaches steady-state after approximately 70 days. A post-hoc sensitivity analysis showed that 77% (n=20/26) of the patients receiving TAKHZYRO 300 mg every two weeks were attack-free during steady-state (day 70-182) vs. 3% of patients on placebo (n=1/37).
Based on an exploratory endpoint, a clinically meaningful improvement in quality of life was observed in 81% of patients treated with TAKHZYRO 300 mg every two weeks compared to 37% of patients in the placebo group [assessed by the Angioedema Quality of Life Questionnaire (AE-QoL)]. The AE-QoL measures the impact of angioedema over a four-week period across four domains: fear/shame, functioning, fatigue/mood, and nutrition.
Henrik Balle Boysen, Executive Director for HAEi said, “On behalf of the HAE community, we welcome today’s news that provides a new option for the prevention of HAE attacks. We are grateful for the time and effort put forth by the patients and researchers who participated in the clinical program that enabled this important addition to the HAE treatment landscape.”
TAKHZYRO has a half-life of approximately two weeks and may be self-administered as one subcutaneous injection every two weeks. In clinical trials, the majority of patients took within 10 to 60 seconds to administer the injection.
Orphan Drug Designation has been maintained by the European Commission.
TAKHZYRO also received approval for the prevention of HAE attacks in people 12 years of age and older in the U.S. on 23 August 2018 and Canada on 19 September 2018. For full U.S. Prescribing Information, including the approved indication and important safety information, please visit https://www.shirecontent.com/PI/PDFs/TAKHZYRO_USA_ENG.pdf. For full Canada Prescribing Information within Canadian Product Monograph, please visit https://www.shirecanada.com/-/media/shire/shireglobal/shirecanada/pdffiles/product%20information/takhzyro-pm-en.pdf.
The HELP Study™
The HELP (Hereditary Angioedema Long-term Prophylaxis) Study™ was a multicentre, randomised, double-blind, placebo-controlled parallel group trial that evaluated the efficacy and safety of subcutaneously administered TAKHZYRO vs. placebo over 26 weeks in 125 patients 12 years of age or older with HAE.
The primary endpoint of the HELP Study™ was the number of investigator-confirmed HAE attacks over the entire 26-week study duration. TAKHZYRO demonstrated that subcutaneous injections every two or four weeks reduced the mean monthly number of attacks across all three TAKHZYRO treatment arms studied: 300 mg every two weeks, 300 mg every four weeks, and 150 mg of TAKHZYRO every four weeks.
Complete results from the Phase 3 HELP Study™ were published in the Journal of the American Medical Association (JAMA) on 27 November 2018.