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Vyvanse (lisdexamfetamine dimesylate) Capsules, (CII) Now Approved in the US for Maintenance Treatment in Adults with ADHD

PHILADELPHIA, February 7, 2012 /PRNewswire/ -- Vyvanse (lisdexamfetamine dimesylate), an approved treatment for Attention-Deficit/Hyperactivity Disorder (ADHD) in patients ages 6 and above, is the first medication both proven to work and approved for maintenance treatment in adults with ADHD.

Shire plc, the global specialty biopharmaceutical company, today announced that the US Food and Drug Administration (FDA) approved the prescription medication Vyvanse (lisdexamfetamine dimesylate) Capsules, (CII) as a maintenance treatment for adults with ADHD. The approval is based on results from a randomized withdrawal study designed to evaluate the efficacy of Vyvanse in adults (aged 18 to 55 years) who were receiving treatment with Vyvanse for a minimum of 6 months prior to enrolling in the study. Significantly more patients treated with Vyvanse maintained ADHD symptom control compared with placebo as determined by the proportion of patients who met criteria for relapse of symptoms at end point during the six-week randomized double-blind withdrawal phase of the study (8.9% of Vyvanse-treated patients vs 75% for placebo). This new approval adds to the indication for Vyvanse as a treatment for ADHD in patients ages 6 and above.

Vyvanse should be used as part of a total treatment program that may include counseling or other therapies. The physician who elects to use Vyvanse for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient.

In a randomized withdrawal design, patients who respond to a treatment are randomized to continue receiving that treatment or placebo. Utilizing the proportion of patients experiencing symptom relapse as a primary outcome, this type of study in patients with ADHD can be used to demonstrate long-term efficacy in lieu of conducting a long-term placebo-controlled, parallel-group study. The utility of this design is that the period of placebo exposure, with the potential for worsening of ADHD symptoms, is relatively short. "Data from this study and the resulting approval illustrate that Vyvanse can help adults with ADHD maintain symptom control. Vyvanse is the first medicine both proven to work and approved to maintain efficacy in adults with ADHD" said Jeffrey Jonas, MD, Senior Vice President of Research and Development for Shire's Specialty Pharmaceuticals and Regenerative Medicine businesses. "This underscores Shire's commitment to providing important advances in the treatment of individuals with ADHD by investing in innovative research in this area," added Dr. Jonas.

Vyvanse is a Schedule II controlled substance. Stimulants, such as amphetamines and methylphenidates, are subject to misuse, abuse, addiction, and criminal diversion. Misuse of amphetamines may cause sudden death and serious cardiovascular adverse events.

This Phase 4, double-blind, multi-center, placebo-controlled, randomized withdrawal design study assessed the maintenance of efficacy and safety of Vyvanse in 123 adults who met DSM-IV-TR® criteria for ADHD. Prior to enrollment, patients were required to have documented long-term treatment with Vyvanse (30, 50, or 70 mg/day) for at least 6 months and demonstrated treatment response as defined by an ADHD Rating Scale IV (ADHD-RS-IV) with adult prompts total score of <22 and Clinical Global Impressions-Severity (CGI-S) ratings <3. After screening, eligible patients entered a three-week open-label treatment phase in which they continued to receive the same Vyvanse dose they were taking at study entry. Following this open-label treatment, patients who maintained treatment response at week 3 entered the six-week double-blind, randomized withdrawal phase (n=116), in which they received on-going treatment with the same dose of Vyvanse (n=56), or switched to placebo (n=60). The ADHD-RS-IV with adult prompts is a clinician assessment of the severity of the core symptoms of ADHD. The CGI-S is a clinician assessment of symptom severity.

The primary efficacy outcome measure was the proportion of patients who met criteria for relapse of ADHD symptoms at end point during the double-blind, randomized withdrawal phase. End point was defined as the last post-randomization treatment week at which a valid ADHD-RS with adult prompts total score and CGI-S were observed. Relapse of ADHD symptoms was defined as a ≥50% increase (worsening) in the ADHD-RS-IV with adult prompts total score and a ≥2-point increase in the CGI-S score compared to scores at entry into the double-blind randomized withdrawal phase. Patients who met criteria for relapse of ADHD symptoms were immediately discontinued from the study.

On the primary efficacy measure, significantly fewer patients met criteria for symptom relapse with Vyvanse (8.9%) versus placebo (75%) (P<.0001) at end point of the randomized withdrawal phase. The majority (approximately 62%) of placebo treated patients who met criteria for relapse of ADHD symptoms did so within 2 weeks following randomization.

During the open-label phase, seven patients discontinued from the study, including one patient on Vyvanse who discontinued due to a treatment-emergent adverse event (TEAE) (lack of efficacy). One serious adverse event (SAE) was reported during the randomized withdrawal phase in a patient receiving placebo (suicidal ideation). No SAEs were reported in patients receiving Vyvanse, and no deaths were reported. During the randomized withdrawal phase, 48.2% (27/56) of patients receiving Vyvanse and 30% (18/60) on placebo reported TEAEs. The most common (≥2%) TEAEs reported in the Vyvanse treatment group included headache, upper respiratory tract infection, insomnia, fatigue and joint sprain. Mean systolic and diastolic blood pressure and pulse rate were slightly higher for Vyvanse-treated patients compared to placebo-treated patients. Small changes in mean blood pressure and pulse rate were observed from baseline to week 3 in the open-label phase and at end point of the randomized withdrawal phase for both Vyvanse and placebo treatment groups. The safety profile seen in this study was consistent with that of other studies of Vyvanse. No new clinically relevant safety signals were associated with abrupt discontinuation of Vyvanse.

"The finding from this study is important because adult patients with ADHD may have a need for extended treatment, and could benefit from a treatment option proven to maintain efficacy," stated Matthew Brams, MD, Principal Investigator and Clinical Assistant Professor of Psychiatry at Baylor College of Medicine. "This study showed that in patients with ADHD who were stable on Vyvanse for 6 months, 91% randomized to receive Vyvanse continued to maintain symptom control compared with 25% taking placebo."

About Vyvanse (lisdexamfetamine dimesylate)

Vyvanse, which was introduced in the United States in July 2007 for the treatment of ADHD in children ages 6 to 12 years, approved in April 2008 to treat ADHD in adults, and approved in November 2010 to treat ADHD in adolescents ages 13 to 17, is currently available in six once-daily dosage strengths of 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, and 70 mg.

Additional information about Vyvanse is available at http://www.vyvanse.com.

Indication

Vyvanse is indicated for the treatment of ADHD in patients ages 6 and above as part of a total treatment plan that may include other measures (psychological, educational, social). Efficacy was established in short-term controlled studies in children aged 6 to 17 and adults. Vyvanse is also approved as a maintenance treatment for adults with ADHD based on one randomized withdrawal study. Extended use of Vyvanse should be periodically reevaluated to determine its long-term usefulness for the individual patient.

Important Safety Information

WARNING: POTENTIAL FOR MISUSE, ABUSE, ADDICTION, AND DIVERSION

See Full Prescribing Information for complete Boxed WARNING.

• Vyvanse is a Schedule II controlled substance. Stimulants, such as amphetamines and methylphenidates, are subject to misuse, abuse, addiction, and criminal diversion.

• Misuse of amphetamines may cause sudden death and serious cardiovascular adverse events.

• Contraindications: Known hypersensitivity to amphetamines or other ingredients in Vyvanse.
Anaphylactic reactions, Stevens-Johnson Syndrome, angioedema, and urticaria have been observed in postmarketing reports. Using Vyvanse with monoamine oxidase inhibitors (MAOIs) can result in hypertensive crisis. Stop MAOIs at least 14 days prior to Vyvanse use.

• Sudden death, stroke and myocardial infarction have been reported with stimulants at usual doses for the treatment of ADHD. Stimulants generally should not be used in patients with known structural cardiac abnormalities or other serious heart problems. Adults have a greater likelihood than children of having such cardiac disease. Patients being considered for stimulant treatment should have a careful history (including family history of sudden death or ventricular arrhythmia) and physical exam to assess for the presence of cardiac disease. Further evaluation should be conducted if needed (eg, electrocardiogram and echocardiogram). Patients who develop symptoms suggestive of cardiac disease (eg, exertional chest pain, unexplained syncope) during stimulant treatment should undergo a prompt evaluation.

• Use with caution in patients whose underlying medical condition might be compromised by increases in blood pressure or heart rate. Stimulants cause modest increases in average blood pressure (about 2-4 mmHg) and average heart rate (about 3-6 bpm) and patients may have larger increases. Monitor all patients for larger changes.

• Use of stimulants may cause psychotic or manic symptoms in patients with no prior history, or exacerbation of symptoms in patients with pre-existing psychosis. Clinical evaluation for bipolar disorder is recommended prior to stimulant use. Monitor for aggressive behavior.

• Monitor growth in children during treatment with Vyvanse. Children who are not growing (gaining height or weight) as expected may need to have their treatment interrupted.

• Stimulants may lower the convulsive threshold. Discontinue if seizures develop.

• Visual disturbances and exacerbation of tics and Tourette's syndrome have been reported with stimulant treatment.

• The most common adverse reactions (≥5% and at least twice the rate of placebo) reported in clinical trials were:

About ADHD

Attention-Deficit/Hyperactivity Disorder is a neurobehavioral disorder that manifests as a persistent pattern of inattention and/or hyperactivity-impulsivity and is more frequent and severe than is typically observed in individuals at a comparable level of development.

ADHD is one of the most common childhood psychiatric disorders. Although many people tend to think of ADHD as a childhood problem, 60% to 85% of children with ADHD may continue to meet the criteria for the disorder during their teenage years. Nearly 50% of children with ADHD may continue to meet the criteria for the disorder into adulthood, based on parent-report. The disorder is estimated to affect 4.4 percent of US adults aged 18 to 44 based on results from the National Comorbidity Survey Replication. When this percentage is extrapolated to the full US population aged 18 and over, approximately 10 million adults are estimated to have ADHD.

The specific etiology of ADHD is unknown, and there is no single diagnostic test for this disorder. Adequate diagnosis requires the use of medical and special psychological, educational, and social resources, utilizing diagnostic criteria specified in the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR®) or International Classification of Diseases, 10th revision (ICD-10).

Although there is no cure for ADHD, there are accepted treatments that have been demonstrated to improve symptoms. Standard treatments include educational approaches, psychological therapies which may include behavioral modification, and/or medication. Ongoing assessment and treatment may be necessary.

Shire plc

Shire's strategic goal is to become the leading specialty biopharmaceutical company that focuses on meeting the needs of the specialist physician. Shire focuses its business on attention deficit hyperactivity disorder, human genetic therapies, gastrointestinal diseases and regenerative medicine as well as opportunities in other therapeutic areas to the extent they arise through acquisitions. Shire's in-licensing, merger and acquisition efforts are focused on products in specialist markets with strong intellectual property protection and global rights. Shire believes that a carefully selected and balanced portfolio of products with strategically aligned and relatively small-scale sales forces will deliver strong results.

For further information on Shire, please visit the Company's website: http://www.shire.com.

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

Statements included herein 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, the Company's results could be materially adversely affected. The risks and uncertainties include, but are not limited to, risks associated with: the inherent uncertainty of research, development, approval, reimbursement, manufacturing and commercialization of the Company's Specialty Pharmaceuticals, Human Genetic Therapies and Regenerative Medicine products, as well as the ability to secure new products for commercialization and/or development; government regulation of the Company's products; the Company's ability to manufacture its products in sufficient quantities to meet demand; the impact of competitive therapies on the Company's products; the Company's ability to register, maintain and enforce patents and other intellectual property rights relating to its products; the Company's ability to obtain and maintain government and other third-party reimbursement for its products; and other risks and uncertainties detailed from time to time in the Company's filings with the Securities and Exchange Commission.

For further information please contact:



Investor Relations
Eric Rojas, erojas@shire.com, +1-781-482-0999
Sarah Elton-Farr, seltonfarr@shire.com, +44-1256-894157


Media
Jessica Mann (Corporate), jmann@shire.com, +44-1256-894-280
Gwen Fisher (Specialty Pharma), gfisher@shire.com, +1-484-595-9836


SOURCE Shire plc

Posted: February 2012

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