Labeling Update Based on Maintenance of Efficacy Data from a 38-Week Phase 3 Study
Lexington, Mass. – October 17, 2016 – For U.S. Audiences Only – Shire plc (LSE: SHP, NASDAQ: SHPG) announces an update to the Vyvanse® (lisdexamfetamine dimesylate) labeling to include information regarding the approval of a supplemental New Drug Application (sNDA) by the U.S. Food and Drug Administration (FDA). The labeling will now include maintenance of efficacy data from SPD489-346, the first-ever longer-term pharmacologic study (38 weeks) in adults with moderate to severe binge eating disorder (B.E.D.). Results from SPD489-346, which were announced in July 2015, indicated that Vyvanse (n=136) demonstrated significant maintenance of efficacy compared to placebo (n=131) based upon the primary endpoint of time to relapse (p<0.001). Vyvanse is approved in the U.S. for adults with moderate to severe B.E.D. Vyvanse is not for weight loss. It is not known if Vyvanse is safe and effective for the treatment of obesity.
“The FDA approval for the labeling update to include maintenance of efficacy data from the first-ever longer-term pharmacologic study in adults with moderate to severe B.E.D. advances our understanding of the efficacy and safety profile of Vyvanse for adults living with the disorder,” said Philip J. Vickers, Ph.D., Global Head of Research and Development at Shire. “Collectively, the data and labeling update represent Shire’s commitment to supporting patients and the health care community by expanding the growing body of research on B.E.D. with longer-term data in this disorder.”
In the 26-week, double-blind, placebo-controlled, randomized-withdrawal phase of this study, relapse was defined as having two or more binge days per week for two consecutive weeks prior to any visit and an increase in Clinical Global Impressions-Severity (CGI-S) score of two or more points relative to the randomized-withdrawal baseline visit. At the conclusion of the study, maintenance of efficacy for patients who had an initial response to Vyvanse during the open-label treatment phase, and then continued on Vyvanse during the randomized-withdrawal phase, was demonstrated with Vyvanse being superior over placebo as measured by time to relapse. The safety profile for Vyvanse in this study, which evaluated treatment-emergent adverse events (TEAEs) and vital signs, was generally consistent with the known profile reported in previous studies in adult patients with moderate to severe B.E.D.
Vyvanse is a federally controlled substance (CII) because it can be abused or lead to dependence. Keep Vyvanse in a safe place to prevent misuse and abuse. Selling or giving away Vyvanse may harm others, and is against the law.
“These data help health care professionals make more informed decisions when discussing treatment options for B.E.D. in adults,” said Susan L. McElroy, M.D., Professor of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine. “Further, the updated Vyvanse labeling with this longer-term maintenance of efficacy data will offer health care professionals a better understanding of how the medication may be incorporated into broader treatment plans for adults with moderate to severe B.E.D.”
Vyvanse is not appropriate for all adults with moderate to severe B.E.D. Adult patients who think they may have symptoms of B.E.D. should talk to their health care professional (HCP). Patients should work with their HCP to develop an appropriate treatment plan.
About The Study
This Phase 3, 38-week, multi-center, double-blind, placebo-controlled, randomized-withdrawal study evaluated the maintenance of efficacy between dose-optimized Vyvanse and placebo based on the primary endpoint of time to relapse in adults aged 18 to 55 (N=267) with moderate to severe B.E.D. A diagnosis of B.E.D. was based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition – Text Revision (DSM-IV-TR®) criteria.
The study consisted of a four-week screening period and a 12-week open-label treatment phase, followed by a 26-week, double-blind, placebo-controlled, randomized-withdrawal phase. During the four-week dose-optimization period, all patients were initiated on Vyvanse 30 mg per day, and then titrated weekly in 20 mg increments to their optimal dose (either 50 mg or 70 mg per day). Patients who met response criteria (one or fewer binge days each week for four consecutive weeks prior to the last visit and had a CGI-S score of two or less at the same visit) at the end of the 12-week open-label phase were randomized to Vyvanse or placebo treatment groups. During this 26-week randomized-withdrawal phase, patients either continued with the same optimized dose of Vyvanse (n=136) from the open-label phase or were switched to placebo (n=131). The primary endpoint was defined as the time to relapse from randomization. Relapse was defined as having two or more binge days per week for two consecutive weeks prior to any visit and an increase in CGI-S score of two or more points relative to the randomized-withdrawal baseline visit. Vyvanse demonstrated superiority over placebo based on the primary endpoint of time to relapse.
The safety profile for Vyvanse in this study, which evaluated TEAEs and vital signs, was generally consistent with the known profile reported in previous studies in adult patients with moderate to severe B.E.D.
During the open-label phase (N=411), three patients experienced serious adverse events (SAEs) and 22 patients reported TEAEs that led to study discontinuation. The most commonly reported TEAEs (reported in 5 percent or more of patients) included dry mouth, headache, insomnia, decreased appetite, nausea, anxiety, constipation, hyperhidrosis, feeling jittery, and diarrhea.
During the randomized-withdrawal phase (Vyvanse, n=136; Placebo, n=134), two patients treated with Vyvanse experienced SAEs and six patients on Vyvanse reported TEAEs that led to study discontinuation. The most commonly reported TEAEs (reported in 5 percent or more of patients) in patients taking Vyvanse included nasopharyngitis, headache, upper respiratory tract infection, and dry mouth, and in patients taking placebo included nasopharyngitis, headache, and fatigue.
Binge eating disorder (B.E.D.), recognized in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5®) as a distinct eating disorder in 2013, is defined as recurring episodes (on average, at least once weekly, for three months) of consuming an unusually large amount of food in a short time, compared with what others would consume under the same or similar circumstances. Adults with B.E.D. feel a sense of lack of control over eating during a binge eating episode and marked distress over their binge eating episodes. They typically experience shame and guilt about their binge eating, among other symptoms, and may conceal their eating problems. Unlike people with other eating disorders, adults with B.E.D. don’t routinely try to “undo” their excessive eating with extreme actions like purging or over-exercising. Only a doctor or other qualified HCP can diagnose B.E.D. and determine an appropriate treatment plan.
B.E.D. is the most common eating disorder among U.S. adults, and is more common than anorexia nervosa and bulimia nervosa combined. The disorder occurs in both men and women, is seen across racial and ethnic groups in U.S. adults, and can occur in normal weight, overweight, and obese adults.
About Vyvanse®(lisdexamfetamine dimesylate)
What is Vyvanse?
Vyvanse is a prescription medicine used for the treatment of moderate to severe binge eating disorder (B.E.D.) in adults. Vyvanse is not for weight loss. It is not known if Vyvanse is safe and effective for the treatment of obesity.
IMPORTANT SAFETY INFORMATION
Vyvanse is a federally controlled substance (CII) because it can be abused or lead to dependence.Keep Vyvanse in a safe place to prevent misuse and abuse. Selling or giving away Vyvanse may harm others, and is against the law.
Vyvanse is a stimulant medicine. Tell the doctor if you have ever abused or been dependent on alcohol, prescription medicines, or street drugs.
Who should not take Vyvanse?
Do not take Vyvanse if you are:
- taking or have taken an anti-depression medicine called a monoamine oxidase inhibitor (MAOI) within the past 14 days
- sensitive or allergic to, or had a reaction to other stimulant medicines
Problems that can occur while taking Vyvanse. Tell the doctor if you:
- have heart problems or heart defects, high blood pressure, or a family history of these problems. This is important because sudden death has occurred in people with heart problems or defects who were taking stimulant medicines, and sudden death, stroke and heart attack have happened in adults taking stimulant medicines. Since increases in blood pressure and heart rate may occur, the doctor should regularly check these during treatment. Call the doctor right away if you have any signs of heart problems such as chest pain, shortness of breath, or fainting while taking Vyvanse.
- have mental problems, or a family history of suicide, bipolar illness, or depression. This is important because new or worsening behavior and thought problems or bipolar illness may occur. New symptoms such as seeing or hearing things that are not real, believing things that are not true, being suspicious, or having new manic symptoms may occur. Call the doctor right away if there are any new or worsening mental symptoms during treatment.
- have circulation problems in fingers and toes (peripheral vasculopathy, including Raynaud’s phenomenon). Fingers or toes may feel numb, cool, painful, sensitive to temperature and/or change color from pale, to blue, to red. Call the doctor right away if any signs of unexplained wounds appear on fingers or toes while taking Vyvanse.
- are pregnant or plan to become pregnant. It is not known if Vyvanse may harm your unborn baby. Are breastfeeding or plan to breastfeed. Do not breastfeed while taking Vyvanse. Talk to your doctor about the best way to feed your baby if you take Vyvanse.
What are possible side effects of Vyvanse?
The most common side effects of Vyvanse reported in studies of adults with moderate to severe B.E.D. include:
For additional safety information, click here for Prescribing Information and Medication Guide and discuss with your doctor.
Vyvanse®is a registered trademark of Shire LLC. Vyvanse is available in 10, 20, 30, 40, 50, 60, and 70 mg capsules.
DSM-IV-TR®and DSM-5®are registered trademarks of the American Psychiatric Association.
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NOTES TO EDITORS
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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