CAMBRIDGE, Massachusetts, February 23, 2017 /PRNewswire/ --
Results Served as Basis for Ongoing Phase 3 Trial
Shire plc (LSE: SHP,NASDAQ: SHPG), the global leader in rare diseases, today announced the publication of results from the Phase 1b study of lanadelumab (SHP643; formerly DX-2930) in the February 23, 2017 issue of the New England Journal of Medicine (NEJM).
Lanadelumab is a subcutaneously administered, human monoclonal antibody that specifically binds and inhibits plasma kallikrein, and it is being investigated for the prevention of angioedema attacks in patients with hereditary angioedema (HAE). HAE is a rare, genetic disorder estimated to affect about 1 in 10,000 to 1 in 50,000 people worldwide. The condition results in recurrent, localized edema (swelling). The areas of the body most commonly affected are the extremities, gastrointestinal tract, and upper airways.,
"In this Phase 1b study, no serious adverse events or discontinuations due to adverse events were observed at all doses studied. Pre-specified efficacy analyses in patients with at least 2 attacks in the 3 months prior to enrolment demonstrated that from day 8 to day 50, the administration of two doses of lanadelumab (300 or 400 mg) 14 days apart, reduced the rate of attacks by 100% and 88% respectively, when compared with placebo. In addition, all subjects were attack-free in the 300 mg group and 82% were attack-free in the 400 mg group, compared to 27% in the placebo group," said Dr. Aleena Banerji, Associate Professor, Massachusetts General Hospital, Boston.
"The overall results of this study are encouraging; it should be noted that while the duration of treatment was relatively short and only a small number of patients were investigated, the results supported further Phase 3 investigations, which are currently ongoing," added Dr. Paula Busse, Associate Professor, Mount Sinai Hospital, New York.
"Despite improvements in the management of HAE in recent years, there is still a need for long-acting prophylactic treatment options. At Shire we are proud of our history in HAE and ongoing commitment to the clinical development of lanadelumab, an investigational prophylactic therapy for this rare genetic disease," said Philip J. Vickers, Ph.D., Global Head of Research and Development at Shire.
The complete publication can be found at nejm.org. The main results were previously presented at the American College of Allergy, Asthma, and Immunology (ACAAI) Annual Scientific Meeting in 2015.
A pivotal Phase 3 trial evaluating the safety and efficacy of lanadelumab as a long-acting prophylactic treatment for HAE is currently underway.
With the clinical development of lanadelumab, Shire is building on its legacy in HAE and as the world leader in rare diseases.
About the Study (NCT02093923)
The multicenter, randomized, double-blind, placebo-controlled, multiple-ascending dose study enrolled a total of 37 patients randomized to receive lanadelumab or placebo across four different dosing groups of 30, 100, 300, or 400 mg. Each subject received two doses of lanadelumab or placebo, separated by 14 days, and was followed for 120 days post-dose. The primary objective of the study was to assess the safety and tolerability of multiple subcutaneous administrations of lanadelumab at different dose levels in HAE patients. Secondary and tertiary objectives included characterization of the pharmacokinetics and pharmacodynamics of lanadelumab, evaluation of immunogenicity, and assessments of HAE attack frequency and use of acute attack therapy.
There were no serious adverse events or discontinuations due to adverse events reported in patients treated with lanadelumab. A total of 29% of the patients who received lanadelumab and 38% of those who received placebo had an adverse event that was considered by trial investigators, who were unaware of the trial-group assignments, to be treatment-related. The most common treatment-related adverse events were injection site pain (25% lanadelumab, 23% placebo) and headache (8% lanadelumab, 15% placebo).
In HAE patients, the pharmacokinetic profile of lanadelumab is linear, dose-dependent, and exhibits a half-life of approximately 14 days, typical of a human monoclonal antibody. The pharmacodynamic profile of lanadelumab was assessed by plasma levels of cleaved high molecular weight kininogen (cHMWK). Pharmacodynamic results confirm plasma kallikrein inhibition in a dose and time-dependent manner, and suggest doses of 300 mg or greater have the potential to normalize cHMWK levels based on levels of cHMWK approaching that observed in healthy subjects.
HAE is a rare genetic disease characterized by recurrent and spontaneous episodes of swelling (edema), typically affecting the extremities, abdomen, face, throat and/or genitourinary tract., Swelling of the throat can be life-threatening due to asphyxiation.- In most cases, the disease is caused by a deficiency of functional C1-esterase inhibitor. This deficiency eventually results in excessive bradykinin production. Bradykinin is a vasodilator responsible for the characteristic symptoms of localized swelling, inflammation, and pain in HAE.
Unopposed activation of the kallikrein-kinin cascade leads to uncontrolled generation of plasma kallikrein, resulting in excessive bradykinin production.
Lanadelumab is an investigational human monoclonal antibody that specifically binds and inhibits plasma kallikrein, and it is being developed for the prevention of angioedema attacks in adult patients with HAE. Lanadelumab is formulated for subcutaneous administration with a half-life of approximately 14 days in patients with HAE.
Shire is the leading global biotechnology company focused on serving people with rare diseases and other highly specialized conditions. We strive to develop best-in-class products, many of which are available in more than 100 countries, across core therapeutic areas including Hematology, Immunology, Neuroscience, Ophthalmics, Lysosomal Storage Disorders, Gastrointestinal / Internal Medicine / Endocrine and Hereditary Angioedema; and a growing franchise in Oncology.
Our employees come to work every day with a shared mission: to develop and deliver breakthrough therapies for the hundreds of millions of people in the world affected by rare diseases and other high-need conditions, and who lack effective therapies to live their lives to the fullest.
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- Longhurst, Hilary. Hereditary Angioedema: Causes, Manifestations and Treatment. British Journal of Hospital Medicine. 2006; 67:654-57
- Cicardi M, et al. Classification, diagnosis and approach to treatment for angioedema: consensus report from the Hereditary Angioedema International Working Group. Allergy. 2014;69(5):602-16
- Bork K, et al. Hereditary angioedema: New findings concerning symptoms, affected organs, and course. Am J Med. 2006; 119(3): 267-74
- Banerji A, et al. Inhibiting Plasma Kallikrein for Hereditary Angioedema Prophylaxis. N Engl J Med 2017;376:717-728
- Bork K, et al. Asphyxiation by laryngeal edema in patients with hereditary angioedema. Mayo Clin Proc. 2000; 75: 349-354
- Bork K, et al. Clinical studies of sudden upper airway obstruction in patients with hereditary angioedema due to C1 esterase inhibitor deficiency. Arch Intern Med. 2003; 163: 1229-1235
- Bork K, et al. Fatal laryngeal attacks and mortality in hereditary angioedema due to C1-INH deficiency. J Allergy Clin Immunol 2012;130:692-7
- Kaplan AP and Joseph K. The bradykinin-forming cascade and its role in hereditary angioedema. Ann Allergy Asthma Immunol 2010;104:193-204.
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