Dublin, Ireland – 27 November 2018 – Shire plc (LSE: SHP, NASDAQ: SHPG), the leading global biotechnology company focused on rare diseases, today announced the Journal of the American Medical Association (JAMA) publication of 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 hereditary angioedema (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. 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.
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. “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.
About 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 lanadelumab versus 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. 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.
Lanadelumab is a fully human monoclonal antibody that specifically binds and decreases the activity of plasma kallikrein. Lanadelumab is produced in Chinese Hamster Ovary (CHO) cells by recombinant DNA technology. Lanadelumab is formulated for subcutaneous administration and has a half-life of approximately two weeks in patients with HAE.
Lanadelumab was approved under the brand name TAKHZYRO™ in the U.S. on 23 August 2018 and Canada on 19 September 2018 and additional regulatory submissions are ongoing worldwide.
U.S. Indication and Important Safety Information
TAKHZYRO (lanadelumab-flyo) is indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in patients ≥12 years of age.
IMPORTANT SAFETY INFORMATION
Hypersensitivity reactions have been observed. In case of a severe hypersensitivity reaction, discontinue TAKHZYRO administration and institute appropriate treatment.
Adverse Reactions: The most commonly observed adverse reactions (≥10% and higher than placebo) associated with TAKHZYRO were injection site reactions consisting mainly of pain, erythema, and bruising at the injection site; upper respiratory infection; headache; rash; myalgia; dizziness; and diarrhea. Less common adverse reactions observed included elevated levels of transaminases; one patient discontinued the trial for elevated transaminases.
Use in Specific Populations: The safety and efficacy of TAKHZYRO in pediatric patients <12 years of age have not been established.
No data are available on TAKHZYRO in pregnant women. No data are available on the presence of lanadelumab in human milk or its effects on breastfed infants or milk production.
To report SUSPECTED ADVERSE REACTIONS, contact Dyax Corp. (a wholly-owned, indirect subsidiary of Shire plc) at 1-800-828-2088, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
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.
Shire’s Commitment to Hereditary Angioedema
Shire is a dedicated, long-term partner to the HAE community with a decade of experience supporting patients. We are committed to serial innovation in HAE and our portfolio of products includes a number of therapy options to help meet the individual needs of those living with the disease. Beyond our focus on developing novel treatments, we provide specialised services and support offerings tailored to the HAE community. Learn more at shire.com.
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Shire is the global biotechnology leader serving patients with rare diseases and specialized conditions. We seek to push boundaries through discovering and delivering new possibilities for patient communities who often have few or no other champions. Relentlessly on the edge of what’s next, we are serial innovators with a diverse pipeline offering fresh thinking and new hope. Serving patients and partnering with healthcare communities in over 100 countries, we strive to be part of the entire patient journey to enable earlier diagnosis, raise standards of care, accelerate access to treatment, and support patients. Our diverse portfolio of therapeutic areas includes Immunology, Hematology, Genetic Diseases, Neuroscience, Internal Medicine and Ophthalmics.
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