Market Overview

Vyvanse® (lisdexamfetamine dimesylate) Positive Top-Line Results in Maintenance of Efficacy Study in Adults with Moderate to Severe Binge Eating Disorder

Share:

Data from This Randomized-Withdrawal Study and a Separate 12-Month Open-Label Safety Extension Study to Be Submitted to FDA in Supplemental New Drug Application (sNDA) by Year End

LEXINGTON, Massachusetts, July 22, 2015 /PRNewswire/ --

For U.S. Audiences Only - Shire plc (LSE: SHP, NASDAQ: SHPG) today reported positive top-line results from a 39-week, long-term maintenance of efficacy study of Vyvanse® (lisdexamfetamine dimesylate) Capsules (CII) in adults with moderate to severe Binge Eating Disorder (B.E.D.).

The objective of the study was to evaluate the maintenance of efficacy between Vyvanse and placebo, based on the primary endpoint of time to relapse of binge eating symptoms in adults (aged 18 to 55) with moderate to severe B.E.D. During the 26-week, double-blind, randomized-withdrawal phase of the study, Vyvanse demonstrated superiority over placebo (p<0.001) on the primary efficacy endpoint of time to relapse. Additionally, at the conclusion of the study, the group continuing on Vyvanse had a significantly lower proportion of relapse (5/136, 3.7%) as compared to the placebo group (42/131, 32.1%).

Based on these results, as well as findings from a separate 12-month open-label safety extension study, the Company plans to submit a supplemental New Drug Application to the U.S. Food and Drug Administration by year end. The FDA will evaluate adding these data to the current labeling for Vyvanse.

"I am very encouraged by these new data because relapse of binge eating symptoms is an important and meaningful consideration for adults with moderate to severe binge eating disorder," said James I. Hudson, M.D., Sc.D., Professor of Psychiatry, Harvard Medical School, Director of the Biological Psychiatry Laboratory at McLean Hospital, Belmont, Mass., and principal investigator for the long-term maintenance of efficacy study, known as SPD489-346.

Vyvanse is approved in the U.S. for the treatment of moderate to severe 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.

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. 

In a separate, 12-month open-label safety extension study (SPD489-345) in adults with moderate to severe B.E.D., the safety profile for Vyvanse was generally consistent with that currently outlined in the United States Prescribing Information (USPI). During the 52-week open-label treatment phase, 17 patients treated with Vyvanse experienced serious adverse events (SAEs) and 54 patients on Vyvanse had treatment-emergent adverse events (TEAEs) that led to study discontinuation. The most commonly reported TEAEs in patients taking Vyvanse (reported in 5% or more of patients) included dry mouth, headache, insomnia, upper respiratory tract infection, nasopharyngitis, constipation, nausea, decreased appetite, irritability, bruxism, sinusitis, anxiety and feeling jittery.

"To our knowledge, Shire is the first to conduct a randomized-withdrawal study assessing pharmacotherapy in adults with moderate to severe B.E.D. This exemplifies our continued commitment to further understanding and addressing the needs of adults with this disorder," said Philip J. Vickers, Ph.D., Head of Research and Development, Shire. "We look forward to working with the FDA as they evaluate the data."

In 2013, the American Psychiatric Association (APA) recognized B.E.D., the most common eating disorder in US adults, as a distinct medical condition. The disorder occurs in both men and women, is seen across racial and ethnic groups, and can occur in normal weight, overweight and obese adults. Medication is not appropriate for all adults with B.E.D.

About The Studies  

Study SPD489-346 

This Phase 3, 39-week, multi-center, placebo-controlled, double-blind, dose-optimized, randomized-withdrawal design study evaluated the maintenance of efficacy between Vyvanse and placebo based on the primary endpoint of time to relapse of binge eating symptoms in adults with moderate to severe B.E.D. (N= 418) based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition - Text Revision (DSM-IV-TR®) criteria.

The study consisted of a 4-week screening period, a 12-week open-label treatment phase        (4 weeks of dose optimization and 8 weeks of maintenance), followed by a 26-week, double-blind, randomized-withdrawal phase and a follow-up visit one week after the last on-treatment visit. During the dose-optimization period, all Vyvanse-treated patients were initiated at the 30-mg dose, and then titrated in 20-mg increments to their optimal dose (either 50-mg or 70-mg). Patients who met "response" criteria (one or fewer binge days each week for four consecutive weeks prior to the last visit at the end of the 12-week open-label phase and had a Clinical Global Impression-Severity [CGI-S] score of two or less at the same visit) were randomized to Vyvanse or placebo treatment groups. During this randomized-withdrawal phase, patients (N=275) received either ongoing treatment with the same optimized dose of Vyvanse from the open-label phase (N=137) or placebo (N=138).

The primary endpoint was defined as the time to relapse of binge eating symptoms during the randomized phase. Relapse was defined as a two or more point increase (worsening) in the investigator's assessment of CGI-S score from the randomization baseline and two or more binge eating days per week in each week for two consecutive weeks prior to the visit. Vyvanse demonstrated superiority over placebo (p<0.001) on the primary efficacy endpoint of time to relapse. Additionally, at the conclusion of the study, the group continuing on Vyvanse had a significantly lower proportion of relapse of (5/136, 3.7%) as compared to the placebo group (42/131, 32.1%).

Safety and tolerability evaluations of Vyvanse included TEAEs and vital signs. The safety profile for Vyvanse in this study was generally consistent with the known profile reported in previous studies in adult patients with moderate to severe B.E.D.

During the 12-week open-label phase of the study, three patients treated with Vyvanse experienced SAEs and 22 patients on Vyvanse had TEAEs that led to study discontinuation. The most commonly reported TEAEs in patients taking Vyvanse (reported in 5% or more of patients) included dry mouth, headache, insomnia, decreased appetite, nausea, anxiety, constipation, hyperhidrosis, feeling jittery and diarrhea.

During the randomized-withdrawal phase, two patients treated with Vyvanse experienced SAEs and six patients on Vyvanse had TEAEs that led to study discontinuation. The most commonly reported TEAEs (reported in 5% 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. Further evaluation of the safety information is currently underway.

Study SPD489-345 

This Phase 3, 53-week, multi-center, open-label extension, dose-optimized study was designed to assess the safety and tolerability of Vyvanse in adults with moderate to severe B.E.D. based on DSM-IV-TR® criteria (N= 604). Subjects enrolled were from previously completed double-blind, placebo-controlled studies.

The study consisted of a 4-week dose-optimization period, a 48-week maintenance period, and a follow-up visit 1 week after the last on-treatment visit.  

Safety and tolerability evaluations included TEAEs, response to the Columbia-Suicide Severity Rating Scale (C-SSRS), vital signs, weight and waist circumference, clinical laboratory evaluations, and electrocardiogram (ECG) results.

During the 52-week open-label treatment phase, 17 patients treated with Vyvanse experienced SAEs and 54 patients on Vyvanse had TEAEs that led to study discontinuation. The most commonly reported TEAEs in patients taking Vyvanse (reported in 5% or more of patients) included dry mouth, headache, insomnia, upper respiratory tract infection, nasopharyngitis, constipation, nausea, decreased appetite, irritability, bruxism, sinusitis, anxiety and feeling jittery.

The safety profile for Vyvanse in this study was generally consistent with that currently outlined in the United States Prescribing Information (USPI).

Shire anticipates presenting the data from studies SPD489-346 and SPD489-345 at future scientific meetings.

About B.E.D. 

Binge Eating Disorder (B.E.D.), recognized as a distinct disorder in 2013 by the APA, is defined as recurring episodes (on average, at least once weekly, for 3 months) of consuming a large amount of food in a short time, compared with what others would consume under the same or similar circumstances. Patients feel a sense of lack of control over eating during a binge eating episode and marked distress over their binge eating. They typically experience shame and guilt, among other symptoms, about their binge eating, and may conceal the symptoms. 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. Adults with moderate to severe B.E.D. usually binge four to thirteen times per week.  Only a doctor or other trained health care professional (HCP) can diagnose B.E.D. and determine an appropriate treatment plan.

B.E.D. is the most common eating disorder in U.S. adults and is more prevalent than anorexia and bulimia combined. The disorder occurs in both men and women, is seen across racial and ethnic groups, and can occur in normal weight, overweight, and obese adults. Medication is not appropriate for all adults with B.E.D.

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, and sudden death, stroke and heart attack have happened in adults. 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, breast-feeding, or plan to become pregnant or breast-feed.

What are possible side effects of Vyvanse (lisdexamfetamine dimesylate)? 

The most common side effects of Vyvanse reported in studies of adults with moderate to severe B.E.D. include:
    
- dry mouth            
- trouble sleeping     
- decreased appetite
- increased heart rate 
- constipation
- feeling jittery
- anxiety







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® is a registered trademark of the American Psychiatric Association.

About Shire 

Shire enables people with life-altering conditions to lead better lives.

Our strategy is to focus on developing and marketing innovative specialty medicines to meet significant unmet patient needs.

We focus on providing treatments in Rare Diseases, Neuroscience, Gastrointestinal and Internal Medicine and are developing treatments for symptomatic conditions treated by specialist physicians in other targeted therapeutic areas, such as Ophthalmics.

http://www.shire.com

THE "SAFE HARBOR" STATEMENT UNDER THE PRIVATE SECURITIES LITIGATION REFORM ACT OF 1995 

Statements included in this announcement that are not historical facts are forward-looking statements. Such forward-looking statements involve a number of risks and uncertainties and are subject to change at any time. In the event such risks or uncertainties materialize, Shire's results could be materially adversely affected. The risks and uncertainties include, but are not limited to, that:

  • Shire's products may not be a commercial success;
  • product sales from ADDERALL XR® and INTUNIV® are subject to generic competition;
  • the failure to obtain and maintain reimbursement, or an adequate level of reimbursement, by third-party payers in a timely manner for Shire's products may affect future revenues, financial condition and results of operations;
  • Shire conducts its own manufacturing operations for certain of its products and is reliant on third-party contract manufacturers to manufacture other products and to provide goods and services. Some of Shire's products or ingredients are only available from a single approved source for manufacture. Any disruption to the supply chain for any of Shire's products may result in Shire being unable to continue marketing or developing a product or may result in Shire being unable to do so on a commercially viable basis for some period of time;
  • the manufacture of Shire's products is subject to extensive oversight by various regulatory agencies. Regulatory approvals or interventions associated with changes to manufacturing sites, ingredients or manufacturing processes could lead to significant delays, an increase in operating costs, lost product sales, an interruption of research activities or the delay of new product launches;
  • Shire has a portfolio of products in various stages of research and development. The successful development of these products is highly uncertain and requires significant expenditures and time, and there is no guarantee that these products will receive regulatory approval;
  • the actions of certain customers could affect Shire's ability to sell or market products profitably. Fluctuations in buying or distribution patterns by such customers can adversely affect Shire's revenues, financial condition or results of operations;
  • investigations or enforcement action by regulatory authorities or law enforcement agencies relating to Shire's activities in the highly regulated markets in which it operates may result in significant legal costs and the payment of substantial compensation or fines;
  • adverse outcomes in legal matters and other disputes, including Shire's ability to enforce and defend patents and other intellectual property rights required for its business, could have a material adverse effect on Shire's revenues, financial condition or results of operations;
  • Shire faces intense competition for highly qualified personnel from other companies and organizations. Shire is undergoing a corporate reorganization and was the subject of an unsuccessful acquisition proposal and the consequent uncertainty could adversely affect Shire's ability to attract and/or retain the highly skilled personnel needed for Shire to meet its strategic objectives;
  • failure to achieve Shire's strategic objectives with respect to the acquisition of NPS Pharmaceuticals Inc. may adversely affect Shire's financial condition and results of operations;

and other risks and uncertainties detailed from time to time in Shire's filings with the U.S. Securities and Exchange Commission, including its most recent Annual Report on Form 10-K.

For further information please contact:
Investor Relations
Sarah Elton-Farr
seltonfarr@shire.com
+44(0)1256-894157

Media
Scott Santiamo
ssantiamo@shire.com
+1-484-343-2576












SOURCE Shire plc

View Comments and Join the Discussion!