26th Feb 2007 07:00
Shire and New River Pharmaceuticals Announce FDA Approval of the First and OnlyStimulant Prodrug VYVANSE¢â€ž¢ (lisdexamfetamine dimesylate) as a Novel Treatmentfor ADHDBasingstoke, U.K., Philadelphia, PA and Radford, VA - FEBRUARY 23, 2007 - Shireplc and its collaborative partner New RiverPharmaceuticals Inc. announced today that the U.S. Food and DrugAdministration (FDA) has granted marketing approval for VYVANSE(lisdexamfetamine dimesylate, formerly known as NRP104), for the treatment ofAttention 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 thebody. In clinical studies designed to measure duration of effect, VYVANSEprovided significant efficacy compared to placebo for a full treatment day, upthrough and including 6:00 pm. Furthermore, when VYVANSE was administeredorally and intravenously in two clinical human drug abuse studies, VYVANSEproduced subjective responses on a scale of "Drug Liking Effects" (DLE) thatwere less than d-amphetamine at equivalent doses. DLE is used in clinical abusestudies to measure relative preference among known substance abusers."The FDA approval of VYVANSE is exciting news for Shire as well as forpatients, their families, and healthcare providers as it's an important, novelapproach for the treatment of ADHD," said Matthew Emmens, Shire Chief ExecutiveOfficer. "The label we received with the approval letter includes informationabout the extended duration of effect and abuse-related drug likingcharacteristics of VYVANSE which illustrate benefits that differentiate thiscompound from other ADHD medicines. The addition of VYVANSE to our ADHDportfolio reaffirms Shire's commitment to continue to address unmet medicalneeds and advance the science of ADHD treatment. Beginning with product launchin Q2 2007, Shire will make VYVANSE our top promotional priority within ourADHD portfolio."Randal J. Kirk, New River's Chairman and Chief Executive Officer, remarked,"VYVANSE's approval signals a new era in the treatment of ADHD. Upon productlaunch, patients will have a novel treatment option combining the effectivenessof a stimulant - long considered the gold standard in ADHD medicines - withother potential benefits."The FDA has proposed that VYVANSE be classified as a Schedule II controlledsubstance. This proposal was submitted to and accepted by the U.S. DrugEnforcement Administration (DEA). A final scheduling decision is expected fromthe DEA following a 30-day period for public comment. Once VYVANSE receivesfinal scheduling designation, the label will be available. Pending finalscheduling designation, product launch is anticipated in Q2 2007. VYVANSE willbe available in three dosage strengths: 30 mg, 50 mg and 70 mg, all indicatedfor once-daily dosing.1New River developed VYVANSE as a new ADHD medication designed to provide lowerpotential for abuse, in which d-amphetamine is covalently linked to l-lysine, anaturally occurring amino acid. The combination is rapidly absorbed from thegastrointestinal tract and converted to d-amphetamine, which is responsible forVYVANSE's activity.Joseph Biederman, MD, director of Pediatric Psychopharmacology at MassachusettsGeneral Hospital, was lead investigator on the pivotal clinical studies testinglisdexamfetamine dimesylate for the treatment of ADHD. These large multi-sitestudies showed that the drug significantly reduced ADHD symptoms throughout theday with a predictable tolerability profile. "Our studies showed that thisnext-generation stimulant medication's unique chemical profile offers an optionfor physicians and their patients in the treatment of ADHD, with outstandingefficacy and duration of action" 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 significantlyimproved behavior when receiving either VYVANSE or ADDERALL XR‚® (mixed salts ofa single-entity amphetamine product) as measured by the Swanson, Kotkin, Agler,M. Flynn and Pelham (SKAMP) deportment rating scale, a standardized, validatedclassroom assessment tool used for evaluating the behavioral symptoms of ADHD.3Both treatments resulted in significantly improved behavior versus a placebo (P
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 advanceddisease 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 calledsympathomimetic amines (for example, pseudoephedrine); seizures; glaucoma; ahistory of problems with alcohol or drugs; agitated states; taken a monoamineoxidase inhibitor (MAOI) within the last 14 days.Tell your doctor before using VYVANSE or Adderall XR if you or your child arebeing treated for or have symptoms of depression (sadness, worthlessness, orhopelessness) or bipolar disorder; have abnormal thoughts 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 VYVANSE or 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.VYVANSE and Adderall XR were generally well tolerated in clinical studies. Themost common side effects in studies of VYVANSE included: children - decreasedappetite, difficulty falling asleep, stomachache, and irritability. The mostcommon side effects in studies of Adderall XR included: children - decreasedappetite, difficulty falling asleep, stomachache, and emotional lability;adolescents - loss of appetite, difficulty falling asleep, stomachache, andweight 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 Tourette'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, andthis press release is neither an offer to purchase nor a solicitation of anoffer to sell New River common stock. Investors and security holders are urgedto read both the tender offer statement and the solicitation/recommendationstatement regarding the tender offer described in this report when they becomeavailable because they will contain important information. The tender offerstatement will be filed by a subsidiary of Shire with the Securities andExchange Commission (SEC), and the solicitation/recommendation statement willbe filed by New River with the SEC. Investors and security holders may obtain afree copy of these statements (when available) and other documents filed byShire or New River with the SEC at the website maintained by the SEC atwww.sec.gov. The tender offer statement and related materials may be obtainedfor free by directing such requests to Shire at Hampshire InternationalBusiness Park, Chineham, Basingstoke, Hampshire, England, RG24 8EP, attention:Investor Relations. The solicitation/recommendation statement and such otherdocuments may be obtained by directing such requests to New River at 1881 GroveAvenue, Radford, Virginia 24141, attention: Director of CorporateCommunications.
For further information on Shire please contact:
Investor Relations Clĩa Rosenfeld (Rest of the World) +44 1256 894 160 Eric Rojas (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
For further information on New River please contact:
The Ruth Group
John Quirk (investors)
646-536-7029
Zack Kubow (media)
646-536-7020
About ADHD
Approximately 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). 10 ADHD is one of the most common psychiatric disorders in children andadolescents. 11 ADHD is a neurobiological disorder that manifests as apersistent pattern of inattention and/or hyperactivity-impulsivity that is morefrequent and severe than is typically observed in individuals at a comparablelevel of development.8 To be properly diagnosed with ADHD, a child needs todemonstrate at least six of nine symptoms of inattention; at least six of ninesymptoms of hyperactivity/impulsivity; the onset of such symptoms before age 7years; that some impairment from the symptoms is present in two or moresettings (e.g., at school and home); that the symptoms continue for at leastsix months; and that there is clinically significant impairment in social,academic or occupational functioning.8
Although there is no "cure" for ADHD, there are accepted treatments that specifically target its symptoms. The most common standard treatments include educational approaches, psychological or behavioral modification, and medication.12
New River
New River Pharmaceuticals Inc. is a specialty pharmaceutical company developingnovel pharmaceuticals that are generational improvements of widely prescribeddrugs in large and growing markets. For further information on New River,please visit the Company's Web site at http://www.nrpharma.com.
"SAFE HARBOR" STATEMENT UNDER THE PRIVATE SECURITIES LITIGATION REFORM ACT OF 1995
This press release contains certain forward-looking information that isintended to be covered by the safe harbor for "forward-looking statements"provided by the Private Securities Litigation Reform Act of 1995. Forward-looking statements are statements that are not historical facts. Words such as"expect(s)," "feel(s)," "believe(s)," "will," "may," "anticipate(s)" andsimilar expressions are intended to identify forward-looking statements. Thesestatements include, but are not limited to, financial projections and estimatesand their underlying assumptions; statements regarding plans, objectives andexpectations with respect to future operations, products and services; andstatements regarding future performance. Such statements are subject to certainrisks and uncertainties, many of which are difficult to predict and generallybeyond the control of New River Pharmaceuticals, that could cause actualresults to differ materially from those expressed in, or implied or projectedby, the forward-looking information and statements. These risks anduncertainties include: those discussed and identified in the New RiverPharmaceuticals Inc. annual report on Form 10-K, filed with the SEC on March15, 2006, as well as other public filings with the SEC; the timing, progressand likelihood of success of our product research and development programs; thetiming and status of our preclinical and clinical development of potentialdrugs; the likelihood of success of our drug products in clinical trials andthe regulatory approval process; our drug products' efficacy, abuse and tamperresistance, resistance to intravenous abuse, onset and duration of drug action,ability to provide protection from overdose, ability to improve patients'symptoms, incidence of adverse events, ability to reduce opioid tolerance,ability to reduce therapeutic variability, and ability to reduce the risksassociated with certain therapies; the ability to develop, manufacture, launchand market our drug products; our projections for future revenues,profitability and ability to achieve certain threshold sales targets; ourestimates regarding our capital requirements and our needs for additionalfinancing; the likelihood of obtaining favorable scheduling and labeling of ourdrug products; the likelihood of regulatory approval under the Federal Food,Drug, and Cosmetic Act without having to conduct long and costly trials togenerate all of the data which are often required in connection with atraditional new chemical entity; our ability to develop safer and improvedversions of widely prescribed drugs using our Carrierwave (TM) technology; oursuccess in developing our own sales and marketing capabilities for our leadproduct candidate; and our ability to obtain favorable patent claims. Readersare cautioned not to place undue reliance on these forward-looking statementsthat speak only as of the date hereof. New River Pharmaceuticals does notundertake any obligation to republish revised forward-looking statements toreflect events or circumstances after the date hereof or to reflect theoccurrence of unanticipated events. Readers are also urged to carefully reviewand consider the various disclosures in New River Pharmaceuticals' annualreport on Form 10-K, filed with the SEC on March 15, 2006, as well as otherpublic filings with the SEC.
Shire plc
Shire's strategic goal is to become the leading specialty pharmaceuticalcompany that focuses on meeting the needs of the specialist physician. Shire focuses itsbusiness on attention deficit and hyperactivity disorder (ADHD), human genetic therapies(HGT),gastrointestinal (GI) and renal diseases. The structure is sufficientlyflexible to allow Shire to target new therapeutic areas to the extent opportunities arise throughacquisitions. Shire believes that a carefully selected portfolio of products with a strategicallyaligned and relatively small-scale sales force will deliver strong results. Shire's focused strategy is to develop and market products for specialty physicians. Shire's in-licensing, merger and acquisition efforts are focused on products in niche markets with strong intellectual property protection either in the US or Europe.
For further information on Shire, please visit the Company's website: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-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 SPD503 (guanfacine extended release) (ADHD), SPD465 (extended releasetriple-bead mixed amphetamine salts) (ADHD); Shire's ability to secure newproducts for commercialization and/or development; Shire's planned acquisitionof New River Pharmaceuticals announced February 20, 2007; and other risks anduncertainties detailed from time to time in Shire's and its predecessorregistrant Shire Pharmaceuticals Group plc's filings with the Securities andExchange Commission, particularly Shire plc's Annual Report on Form 10-K forthe year ended December 31, 2005. # # # 1 data on file2 New River Pharmaceuticals Inc. CONFIDENTIAL CLINICAL STUDY REPORT PROTOCOLNO.; LDX.301 "A Phase 3, Randomized, Multi-Center, Double-Blind,Parallel-Group, Placebo-Controlled Study of LDX in Children Aged 6-12 Yearswith Attention Deficit Hyperactivity Disorder (ADHD)," Final (4.0), 02 November2005.
3 Wigal SB, Gupta S, Guinta S, Swanson JM. Reliability and Validity of the SKAMP Rating Scale in a Laboratory School Setting. Psychopharmacol Bull. 1998l 34 (1): 47-53.
4 "Improvements in Symptoms of Attention-Deficit/Hyperactivity Disorder in School-aged Children with Lisdexamfetamine (NRP104) and Mixed Amphetamine Salts, Extended-Release Versus Placebo," presented at the American Psychiatric Association, Toronto, Ontario, Canada, May 24, 2006.
5 "Efficacy and Safety of Lisdexamfetamine (NRP104) in Children Aged 6 to 12Years With Attention-Deficit/Hyperactivity Disorder (ADHD)," presented at theAmerican Psychiatric Association, Toronto, Ontario, Canada, May 24, 2006.
6 DuPaul G. Parent and Teacher Ratings of ADHD Symptoms: Psychometric Properties in a Community-Based Sample. Journal of Clinical Child Psychology. 1991; 20(3): 245-53.
7 Collett BR, Ohan JL, Meyers KM. Ten Year Review of Rating Scales. V: Scales Assessing Attention-Deficit/Hyperactivity Disorder. Journal of American Academic Child Adolescent Psychiatry. 2003; 42(9): 1015-37.
8 Diagnostic and Statistical Manual of Mental Disorders: Fourth Edition, TextRevision. DSM-TR-IV‚®. Washington, DC: American Psychiatric Association; 2000:85.
9 Childress AC, Krishnan S, McGough JJ, Findling RL. Interim Analysis of a Long-Term, Open-Label, Single-Arm Study of Lisdexamfetamine (LDX), an Amphetamine Prodrug, in children with ADHD. American Academy of Child and Adolescent Psychiatry Annual Meeting; 2006 Oct. 27; San Diego, CA: American Academy of Child and Adolescent Psychiatry; 2006.
10 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, 2005.11 "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.
12 Baumgartel A, et al. Practice guideline for the diagnosis and management of attention deficit hyperactivity disorder. Ambulatory Child Health. 1998;4:51.
Press Release
SHIRE PLCRelated Shares:
Shire