PHILADELPHIA — October 22, 2009 — Shire plc (LSE: SHP, NASDAQ: SHPGY), the global specialty biopharmaceutical company, announced new data about the pharmacokinetics of its Attention-Deficit/Hyperactivity Disorder (ADHD) medication, Vyvanse® (lisdexamfetamine dimesylate) Capsules CII, which showed that Vyvanse provided similar concentrations of its active medication in the blood when administered either intranasally or when administered orally. Specifically, the overall rate and extent of exposure to d-amphetamine, the active medication in Vyvanse, was similar in healthy adults whether they received the drug as a solution through the nose or orally as a capsule. These findings, which were recently presented at a major psychiatric meeting, reflect the ongoing efforts of Shire to further understand the abuse potential of Vyvanse.
“This research is important because the route of administration of a drug may affect the rate and extent of absorption, which in turn may affect the risk of abuse. However, in this study, absorption of Vyvanse through the nose did not result in a rapid rise in d-amphetamine levels,” said Patrick Martin, MD, Vice President, Global Clinical Pharmacology and Pharmacokinetics at Shire. “In this study, exposure to d-amphetamine did not differ when Vyvanse was administered orally or intranasally. While the results of this study are important, it is not accurate to say or imply that Vyvanse cannot be abused.”
Vyvanse is indicated for oral administration only, and should not be administered intranasally.
Vyvanse, which is approved to treat ADHD in children aged 6 to 12 years and in adults, is a therapeutically inactive prodrug, in which d-amphetamine is covalently bonded to l-lysine, and after oral ingestion it is converted to pharmacologically active d-amphetamine. The conversion of Vyvanse to d-amphetamine is not affected by gastrointestinal pH and is unlikely to be affected by alterations in GI transit times. ADHD stimulant products are classified as schedule II controlled substances because a high potential for abuse exists.
About the Study
This open-label, two-period, crossover study compared the pharmacokinetics of d-amphetamine, the active medication derived from Vyvanse, in 18 healthy men after single administration through nasal and oral routes. The primary objectives of the study were to determine whether Vyvanse is absorbed after intranasal delivery and to assess the extent of absorption and conversion to
d-amphetamine, specifically whether administration through the nose would alter the rate and extent of absorption. A secondary study objective was to evaluate the safety of Vyvanse administered as a single oral dose and a single intranasal dose.
In the study, investigators randomly assigned participants to receive a single nasal or oral dose of Vyvanse 50 mg, then, at least seven days later, the subjects received the opposite regimen. Results showed that the rate and extent of d-amphetamine exposure were similar in the healthy participants who received a single 50-mg dose of Vyvanse either through the nose via a solution formulation or orally in capsule form. Specifically, the median time to maximum plasma concentration of d-amphetamine was five hours after oral administration of Vyvanse and four hours after intranasal administration of Vyvanse. Maximum plasma concentration for intranasal administration and oral administration of Vyvanse were similar (35.9 ng/mL versus 37.6 ng/mL, respectively).
In this study, treatment-emergent adverse events were mild to moderate in severity and consistent with known effects of amphetamine. The most common adverse events with an incidence greater than 5 percent among subjects administered Vyvanse by intranasal administration were: tachycardia (two of 18 subjects), dry mouth (two of 18 subjects), and feeling jittery (two of 18 subjects), and for oral administration: anorexia (four of 18 subjects). Adverse events were more common after intranasal administration, reported by 38.9 percent of participants (seven of 18), compared with 27.8 percent of participants (five of 18) after oral administration.
Vyvanse, which was introduced in the United States in July 2007 for the treatment of ADHD in children aged 6 to 12 years and approved in April 2008 to treat ADHD in adults, is currently available in six dosage strengths of 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, and 70 mg.
Additional information about Vyvanse and Full Prescribing Information, including Medication Guide, are available at http://www.vyvanse.com.
For further information please contact:
Media Matthew Cabrey (Shire North America) +1 484 595 8248
Mindy Huber (Porter Novelli for Shire) +1 212 601 8330
IMPORTANT SAFETY INFORMATION about Vyvanse
Vyvanse is indicated for the treatment of ADHD. Efficacy based on two controlled trials in children aged 6 to 12 and one controlled trial in adults.
Vyvanse should not be taken by patients who have advanced arteriosclerosis; symptomatic cardiovascular disease; moderate to severe hypertension; hyperthyroidism; known hypersensitivity or idiosyncrasy to sympathomimetic amines; agitated states; glaucoma; a history of drug abuse; or during or within 14 days after treatment with monoamine oxidase inhibitors (MAOIs).
Sudden death has been reported in association with CNS stimulant treatment at usual doses in children and adolescents with structural cardiac abnormalities or other serious heart problems. Sudden death, stroke, and myocardial infarction have been reported in adults taking stimulant drugs at usual doses in ADHD. Physicians should take a careful patient history, including family history, and physical exam, to assess the presence of cardiac disease. Patients who report symptoms of cardiac disease such as exertional chest pain and unexplained syncope should be promptly evaluated. Use with caution in patients whose underlying medical condition might be affected by increases in blood pressure or heart rate.
New psychosis, mania, aggression, growth suppression, and visual disturbances have been associated with the use of stimulants. Use with caution in patients with a history of psychosis, seizures or EEG abnormalities, bipolar disorder, or depression. Growth should be monitored in children during treatment with stimulants, and patients who are not growing (gaining height or weight) as expected may need to have their treatment interrupted.
Amphetamines have a high potential for abuse. Administration of amphetamines for prolonged periods of time may lead to drug dependence. Particular attention should be paid to the possibility of subjects obtaining amphetamines for non-therapeutic uses or distribution to others and the drugs should be prescribed or dispensed sparingly. Misuse of amphetamine may cause sudden death and serious cardiovascular adverse events.
The most common adverse events reported in clinical studies of Vyvanse were: pediatric — decreased appetite, insomnia, abdominal pain, and irritability; adult ? decreased appetite, insomnia, and dry mouth.
ADHD is one of the most common psychiatric disorders in children and adolescents. Worldwide prevalence of ADHD is estimated at 5.3 percent (with large variability), according to a comprehensive systematic review of this topic published in 2007 in the American Journal of Psychiatry. In the United States, approximately 7.8 percent of all school-aged children, or about 4.4 million children aged 4 to 17 years, have been diagnosed with ADHD at some point in their lives, according to the Centers for Disease Control and Prevention (CDC). The disorder is also 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, almost 10 million adults are believed to have ADHD.
ADHD is a psychiatric behavioral disorder that manifests as a persistent pattern of inattention and/or hyperactivity-impulsivity that is more frequent and severe than is typically observed in individuals at a comparable level of development. 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 such as Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV®) or International Classification of Diseases 10 (ICD-10).
Although there is no cure for ADHD, there are accepted treatments that specifically target its symptoms. Standard treatments include educational approaches, psychological or behavioral modification, and/or medication.
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 (ADHD), human genetic therapies (HGT) and gastrointestinal (GI) diseases 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 Web site: http://www.shire.com.
THE “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 Pharmaceutical and Human Genetic Therapies products, as well as the ability to secure and integrate 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.