Press Release: Shire, New River Pharmaceuticals Announce FDA Approval of VYVANSE
Shire Pharmaceuticals and New River Pharmaceuticals Announce FDA Approval of The First and Only Stimulant Prodrug VYVANSE(TM) as a Novel Treatment for ADHD Basingstoke, U.K., Philadelphia, PA and Radford, VA â€“ FEBRUARY 23, 2007 â€“ Shire plc and its collaborative partner New River Pharmaceuticals Inc. announced today that the U.S. Food and Drug Administration (FDA) has granted marketing approval for VYVANSE (lisdexamfetamine dimesylate, formerly known as NRP104), for the treatment of Attention Deficit Hyperactivity Disorder (ADHD). On February 20, 2007 Shire and New River announced an agreement whereby Shire will acquire New River for approximately $2.6 billion in an all cash transaction unanimously recommended by the Boards of both companies. The transaction is the subject of another press release issued February 20, 2007. VYVANSE is a prodrug that is therapeutically inactive until metabolized in the body. In clinical studies designed to measure duration of effect, VYVANSE provided significant efficacy compared to placebo for a full treatment day, up through and including 6:00 pm. Furthermore, when VYVANSE was administered orally and intravenously in two clinical human drug abuse studies, VYVANSE produced subjective responses on a scale of â€œDrug Liking Effectsâ€ (DLE) that were less than d-amphetamine at equivalent doses. DLE is used in clinical abuse studies to measure relative preference among known substance abusers. â€œThe FDA approval of VYVANSE is exciting news for Shire as well as for patients, their families, and healthcare providers as itâ€™s an important, novel approach for the treatment of ADHD,â€ said Matthew Emmens, Shire Chief Executive Officer. â€œThe label we received with the approval letter includes information about the extended duration of effect and abuse-related drug liking characteristics of VYVANSE which illustrate benefits that differentiate this compound from other ADHD medicines. The addition of VYVANSE to our ADHD portfolio reaffirms Shireâ€™s commitment to continue to address unmet medical needs and advance the science of ADHD treatment. Beginning with product launch in Q2 2007, Shire will make VYVANSE our top promotional priority within our ADHD portfolio.â€ Randal J. Kirk, New Riverâ€™s Chairman and Chief Executive Officer, remarked, â€œVYVANSEâ€™s approval signals a new era in the treatment of ADHD. Upon product launch, patients will have a novel treatment option combining the effectiveness of a stimulant â€“ long considered the gold standard in ADHD medicines â€“ with other potential benefits.â€ The FDA has proposed that VYVANSE be classified as a Schedule II controlled substance. This proposal was submitted to and accepted by the U.S. Drug Enforcement Administration (DEA). A final scheduling decision is expected from the DEA following a 30-day period for public comment. Once VYVANSE receives final scheduling designation, the label will be available. Pending final scheduling designation, product launch is anticipated in Q2 2007. VYVANSE will be available in three dosage strengths: 30 mg, 50 mg and 70 mg, all indicated for once-daily dosing.1 New River developed VYVANSE as a new ADHD medication designed to provide lower potential for abuse, in which d-amphetamine is covalently linked to l-lysine, a naturally occurring amino acid. The combination is rapidly absorbed from the gastrointestinal tract and converted to d-amphetamine, which is responsible for VYVANSEâ€™s activity. Joseph Biederman, MD, director of Pediatric Psychopharmacology at Massachusetts General Hospital, was lead investigator on the pivotal clinical studies testing lisdexamfetamine dimesylate for the treatment of ADHD. These large multi-site studies showed that the drug significantly reduced ADHD symptoms throughout the day with a predictable tolerability profile. â€œOur studies showed that this next-generation stimulant medication's unique chemical profile offers an option for physicians and their patients in the treatment of ADHD, with outstanding efficacy and duration of actionâ€ said Dr. Biederman. Additional information about VYVANSE and other Shire treatments for ADHD is available at www.ShireADHDTreatments.com. VYVANSE Significantly Controls ADHD Symptoms Data from phase II and phase III clinical trials demonstrated statistically significant improvements in ADHD symptoms for patients aged 6 to 12 years treated with VYVANSE compared to patients treated with placebo. These studies demonstrated that all doses of VYVANSE (30 mg, 50 mg and 70 mg) provided significant efficacy at all time points tested, including 6pm.2 In the phase II, analog classroom study, patients demonstrated significantly improved behavior when receiving either VYVANSE or ADDERALL XRÂ® (mixed salts of a single-entity amphetamine product) as measured by the Swanson, Kotkin, Agler, M. Flynn and Pelham (SKAMP) deportment rating scale, a standardized, validated classroom assessment tool used for evaluating the behavioral symptoms of ADHD.3 Both treatments resulted in significantly improved behavior versus a placebo (P <.0001, for both).4 Patients also demonstrated significantly improved academic productivity with both treatments, compared to placebo (P <.0001 for both medications) as measured by Permanent Product Measure of Performance (PERMP), an age-adjusted collection of math problems that measures a childâ€™s ability to pay attention and stay on task as demonstrated by an increase in the number of attempted and successfully completed problems.4 In the phase III, randomized, double-blind placebo-controlled study, all three doses of VYVANSE demonstrated significant improvements in ADHD Rating Scale (ADHD-RS-IV) scores compared with placebo (P <.0001) after four weeks of once-daily treatment. 5 ADHD-RS-IV is a standardized, validated test for assessing symptoms of ADHD in children and for assessing their response to treatment.6,7 This scale, which contains 18 items, is based on the ADHD diagnostic criteria as defined in the APAâ€™s Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text RevisionÂ®, a publication of the American Psychiatric Association. 8 Additionally, in a study presented in October at a major scientific meeting, VYVANSE yielded a 60 percent improvement in the primary rating scale scores for symptoms of ADHD in children aged 6 to 12 years who received six months of treatment in an open-label phase III study. Results also demonstrated that at 6 months, 95 percent of children taking VYVANSE produced a â€œmuch improvedâ€ or â€œvery much improvedâ€ rating on the Clinical Global Impressions â€“ Improvement score.9 About VYVANSE and ADDERALL XR Tell your doctor about any heart conditions, including structural abnormalities, that you, your child, or a family member, may have. Inform your doctor immediately if you or your child develops symptoms that suggest heart problems, such as chest pain or fainting. VYVANSE or Adderall XR should not be taken by patients who have advanced disease of the blood vessels (arteriosclerosis); symptomatic heart disease; moderate to severe high blood pressure; overactive thyroid gland (hyperthyroidism); known allergy or unusual reactions to drugs called sympathomimetic amines (for example, pseudoephedrine); seizures; glaucoma; a history of problems with alcohol or drugs; agitated states; taken a monoamine oxidase inhibitor (MAOI) within the last 14 days. Tell your doctor before using VYVANSE or Adderall XR if you or your child are being treated for or have symptoms of depression (sadness, worthlessness, or hopelessness) or bipolar disorder; have abnormal thoughts or visions, hear abnormal sounds, or have been diagnosed with psychosis; have had seizures or abnormal EEGs; have or have had high blood pressure; exhibit aggressive behavior or hostility. Tell your doctor immediately if any of these conditions or symptoms develop while using VYVANSE or Adderall XR. Abuse of amphetamines may lead to dependence. Misuse of amphetamine may cause sudden death and serious cardiovascular adverse events. These events have also been reported rarely with amphetamine use. VYVANSE and Adderall XR were generally well tolerated in clinical studies. The most common side effects in studies of VYVANSE included: children - decreased appetite, difficulty falling asleep, stomachache, and irritability. The most common side effects in studies of Adderall XR included: children - decreased appetite, difficulty falling asleep, stomachache, and emotional lability; adolescents - loss of appetite, difficulty falling asleep, stomachache, and weight loss; adults - dry mouth, loss of appetite, difficulty falling asleep, headache, and weight loss. Aggression, new abnormal thoughts/behaviors, mania, growth suppression, worsening of motion or verbal tics and Touretteâ€™s syndrome have been associated with use of drugs of this type. Tell your doctor if you or your child have blurred vision while taking VYVANSE or Adderall XR. The Collaboration Agreement In January 2005, New River Pharmaceuticals signed a collaborative agreement with Shire to develop and commercialize VYVANSE. Details on the collaboration agreement are available in previous filings with the U.S. Securities and Exchange Commission. Planned Acquisition Additional Information The tender offer described in this press release has not yet commenced, and this press release is neither an offer to purchase nor a solicitation of an offer to sell New River common stock. Investors and security holders are urged to read both the tender offer statement and the solicitation/recommendation statement regarding the tender offer described in this report when they become available because they will contain important information. The tender offer statement will be filed by a subsidiary of Shire with the Securities and Exchange Commission (SEC), and the solicitation/recommendation statement will be filed by New River with the SEC. Investors and security holders may obtain a free copy of these statements (when available) and other documents filed by Shire or New River with the SEC at the website maintained by the SEC at www.sec.gov. The tender offer statement and related materials may be obtained for free by directing such requests to Shire at Hampshire International Business Park, Chineham, Basingstoke, Hampshire, England, RG24 8EP, attention: Investor Relations. The solicitation/recommendation statement and such other documents may be obtained by directing such requests to New River at 1881 Grove Avenue, Radford, Virginia 24141, attention: Director of Corporate Communications.