9th Oct 2006 07:00
FDA Issues Approvable Letter for NRP104 (lisdexamfetamine dimesylate)for theTreatment of ADHDBasingstoke, U.K., and Philadelphia, U.S. - OCTOBER 6, 2006 - Shire plc (LSE:SHP, NASDAQ: SHPGY, TSX: SHQ) announced today that its collaborative partnerNew River Pharmaceuticals Inc. (NASDAQ: NRPH) has received an approvable letterfrom the U.S. Food and Drug Administration (FDA) for NRP104 (lisdexamfetaminedimesylate), for the treatment of pediatric Attention-Deficit/HyperactivityDisorder (ADHD). This result is generally consistent with historical responsesfrom FDA following their review of New Drug Applications for ADHD medications.According to the FDA's letter, marketing approval of NRP104 is contingent uponfinal scheduling by the U.S. Drug Enforcement Administration (DEA). Noadditional studies have been requested by the FDA as a condition for approvalof NRP104. Shire and New River will continue dialog with FDA officials to agreeupon a final trade name. Shire and New River Pharmaceuticals are preparing fora product launch in Q2 2007, pending final labelling and schedulingdiscussions.The Controlled Substance Staff of the FDA has initially proposed that NRP104 beplaced in Schedule II of the Controlled Substance Act. The initial proposalwill be submitted to the DEA, which is responsible for making a finalscheduling assignment. Shire anticipates timely resolution of this process.Once NRP104 is approved by FDA and the schedule designation is issued by DEA,NRP104 will be available in three dosage strengths: 30 mg, 50 mg and 70 mg, allindicated for once-a-day dosing."This approvable letter for NRP104 is positive news for Shire and our partnerNew River Pharmaceuticals," said Shire Chief Executive Officer Matthew Emmens."Following approval, NRP104 is expected to offer patients, their families, andhealthcare providers an important new treatment for ADHD. As a companyspecializing in the treatment of ADHD, we have a wide range of medications forthis condition currently marketed or under development, including the mostprescribed brand of ADHD medication, ADDERALL XR‚®. Once approved, we lookforward to adding NRP104 to the Shire portfolio."New River Pharmaceuticals designed NRP104 as a new ADHD medication in whichdextro-amphetamine is covalently linked to l-lysine, a naturally occurringamino acid. NRP104, designed to provide efficacy throughout the day up to 6p.m., remains inactive until converted in the body and the active drug isreleased.1In January 2005, New River Pharmaceuticals signed a collaborative agreementwith Shire to develop and commercialize NRP104.The Collaboration AgreementShire plans to file a Current Report on Form 8-K with the U.S. Securities andExchange Commission providing additional details on the company's U.S.collaboration agreement with New River.Under the terms of the agreement with New River, the parties will collaborateon NRP104 development, manufacturing, marketing and sale in the US. New RiverPharmaceuticals will be financially and operationally responsible for clinicaland manufacturing development. Shire will book the product sales and New RiverPharmaceuticals will supply up to 25% of the sales effort under a co promotionright. Shire is obligated to give NRP104 marketing and promotional priorityover its other oral ADHD stimulants should NRP104's label contain a claim thatit has decreased potential for abuse or overdose protection.If NRP104 is approved with a Schedule III, IV or V classification or isunscheduled ("favorable scheduling"), Shire will pay New River a $300 millionmilestone payment. US operating profit will be divided as follows: Shire willretain 75 percent of profits for the first two years following launch, and theparties will share the profits equally thereafter.In the event that NRP104 receives a final Schedule II classification, nomilestone payment will be payable by Shire to New River upon approval. Divisionof profits will be calculated under an alternative profit sharing scheme. NewRiver's share of U.S. product profits for the first two years will be at least25%, though it may increase to a value determined by a preset formula; forfollowing years, it will be at least 50%, though it may increase to a valuedetermined by a preset formula thereafter. These formulas, which include yearlythreshold sales, will be included in the 8-K to be filed.If NRP104 is approved with a Schedule II classification on approval and it getsfavorable scheduling within one year of the first commercial sale, Shire willpay New River a $200 million milestone payment; if favorable scheduling occursby the third anniversary, the milestone payment will be $100 million. Uponfavorable scheduling being achieved under each of these scenarios, the profitsharing formula reverts to that applicable to favorable scheduling from productapproval.In addition, New River will be entitled to a $100 million milestone payment atthe end of the first calendar year in which cumulative worldwide net sales ofall collaboration products during that calendar year exceed $1 billion. Shireintends to capitalize and amortize any milestone payment and sales bonus overthe life of the product.Shire is entitled to terminate the agreement until 30 days following approvalof NRP104. If Shire terminates before regulatory approval, no payment would bedue Shire. If Shire terminates after approval and NRP104 has received afavorable scheduling assignment, no payment would be due Shire. If the approvedNRP104 has received a Schedule II classification, Shire would be entitled to a$50 million termination payment, payable in cash, New River common stock, or anunsecured, 5-year promissory note, as will be agreed upon by Shire and NewRiver.On August 14, 2006 Shire announced that it had settled all pending litigationwith Barr Laboratories, Inc. in connection with Barr's Abbreviated New DrugApplication and its attempt to market generic versions of Shire's ADDERALL XR(extended-release mixed amphetamine salts) for the treatment of ADHD. Barr willnot be permitted to market a generic version of ADDERALL XR in the UnitedStates until April 1, 2009, except under certain limited circumstances, such asthe launch of another party's generic version of ADDERALL XR. -ends- For further information please contact:Investor Clƒ©a Rosenfeld (Rest of the World) +44 1256 894 160Relations Brian Piper (North America) +1 484 595 8252 Media Jessica Mann (Rest of the World) +44 1256 894 280 Matthew Cabrey (North America) +1 484 595 8248 About ADHDApproximately 7.8 percent of all school-age children, or about 4.4 million U.S.children aged 4 to 17 years, have been diagnosed with ADHD at some point intheir lives, according to the U.S. Centers for Disease Control and Prevention(CDC). ADHD is one of the most common psychiatric disorders in children andadolescents. ADHD is a neurobiological disorder that manifests as a persistentpattern of inattention and/or hyperactivity-impulsivity that is more frequentand severe than is typically observed in individuals at a comparable level ofdevelopment. To be properly diagnosed with ADHD, a child needs to demonstrateat least six of nine symptoms of inattention; at least six of nine symptoms ofhyperactivity/impulsivity; the onset of such symptoms before age 7 years; thatsome impairment from the symptoms is present in two or more settings (e.g., atschool and home); that the symptoms continue for at least six months; and thatthere is clinically significant impairment in social, academic or occupationalfunctioning.4Although there is no "cure" for ADHD, there are accepted treatments thatspecifically target its symptoms. The most common standard treatments includeeducational approaches, psychological or behavioral modification, andmedication.For more information about ADHD, please visit www.ShireADHDTreatments.com.About ADDERALL XR (mixed salts of a single-entity amphetamine product)Tell your doctor about any heart conditions, including structuralabnormalities, that you, your child, or a family member, may have. Informyour doctor immediately if you or your child develop symptoms that suggestheart problems, such as chest pain or fainting.ADDERALL XR should not be taken by patients who have advanced disease of theblood vessels (arteriosclerosis); symptomatic heart disease; moderate to severehigh blood pressure; overactive thyroid gland (hyperthyroidism); known allergyor unusual reactions to drugs called sympathomimetic amines (for example,pseudoephedrine); seizures; glaucoma; a history of problems with alcohol ordrugs; agitated states; taken a monoamine oxidase inhibitor (MAOI) within thelast 14 days.Tell your doctor before using ADDERALL XR if you or your child are beingtreated for or have symptoms of depression (sadness, worthlessness, orhopelessness) or bipolar disorder; have abnormal thought or visions, hearabnormal sounds, or have been diagnosed with psychosis; have had seizures orabnormal EEGs; have or have had high blood pressure; exhibit aggressivebehavior or hostility. Tell your doctor immediately if any of these conditionsor symptoms develop while using ADDERALL XR.Abuse of amphetamines may lead to dependence. Misuse of amphetamine may causesudden death and serious cardiovascular adverse events. These events have alsobeen reported rarely with amphetamine use.ADDERALL XR was generally well tolerated in clinical studies. The most commonside effects in studies included: children - decreased appetite, difficultyfalling asleep, stomachache, and emotional lability; adolescents - loss ofappetite, difficulty falling asleep, stomachache, and weight loss; adults -dry mouth, loss of appetite, difficulty falling asleep, headache, and weightloss. Aggression, new abnormal thoughts/behaviors, mania, growth suppression,worsening of motion or verbal tics and Tourette's syndrome have been associatedwith use of drugs of this type. Tell your doctor if you or your child haveblurred vision while taking ADDERALL XR.Shire plcShire's strategic goal is to become the leading specialty pharmaceuticalcompany that focuses on meeting the needs of the specialist physician. Shirefocuses its business on attention deficit and hyperactivity disorder (ADHD),human genetic therapies (HGT), gastrointestinal (GI) and renal diseases. Thestructure is sufficiently flexible to allow Shire to target new therapeuticareas to the extent opportunities arise through acquisitions. Shire believesthat a carefully selected portfolio of products with a strategically alignedand relatively small-scale sales force will deliver strong results.Shire's focused strategy is to develop and market products for specialtyphysicians. Shire's in-licensing, merger and acquisition efforts are focused onproducts in niche markets with strong intellectual property protection eitherin the US or Europe.For further information on Shire, please visit the Company's website: www.shire.com.THE "SAFE HARBOR" STATEMENT UNDER THE PRIVATE SECURITIES LITIGATION REFORM ACTOF 1995Statements included herein that are not historical facts are forward-lookingstatements. Such forward-looking statements involve a number of risks anduncertainties and are subject to change at any time. In the event such risks oruncertainties materialize, Shire's results could be materially affected. Therisks and uncertainties include, but are not limited to, risks associated with:the inherent uncertainty of pharmaceutical research, product development,manufacturing and commercialization; the impact of competitive products,including, but not limited to the impact of those on Shire's Attention Deficitand Hyperactivity Disorder (ADHD) franchise; patents, including but not limitedto, legal challenges relating to Shire's ADHD franchise; government regulationand approval, including but not limited to the expected product approval datesof CONNEXYN (SPD503) (ADHD), SPD465 (ADHD), MESAVANCE (mesalamine) with MMXtechnology (SPD 476) (ulcerative colitis), and NRP104 (ADHD), including itsscheduling classification by the Drug Enforcement Administration in the UnitedStates; Shire's ability to secure new products for commercialization and/ordevelopment; and other risks and uncertainties detailed from time to time inShire's and its predecessor registrant Shire Pharmaceuticals Group plc'sfilings with the Securities and Exchange Commission, particularly Shire plc'sAnnual Report on Form 10-K for the year ended December 31, 2005. # # # 1 Data on file.2 Mental health in the United States: Prevalence of diagnosis and medicationtreatment for attention-deficit/hyperactivity disorder, United States, 2003.MMWR, September 2, 2005;54(34):842-847. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5434a2.htm. Accessed September 27, 2005.3 "Introduction," Diagnosis and Treatment of Attention Deficit HyperactivityDisorder. NIH Consensus Statement 1998 Nov 16-18; 16(2): 1-37. Available at: http://consensus.nih.gov/cons/110/110_statement.htm#0_Abstract. Accessed onJune 8, 2005.4 Diagnostic and Statistical Manual of Mental Disorders: Fourth Edition, TextRevision. DSM-TR-IV‚®. Washington, DC: American Psychiatric Association; 2000:85.5 Baumgartel A, et al. Practice guideline for the diagnosis and management ofattention deficit hyperactivity disorder. Ambulatory Child Health. 1998;4:51.Hampshire International Business Park Chineham Basingstoke Hampshire RG24 8EP United Kingdom Tel +44 (0)1256 894000 Fax +44 (0)1256 894708 www.shire.com Press Release Registered in England 2883758 Registered Office as aboveENDSHIRE PLCRelated Shares:
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