FDA Issues Approvable Letter for SPD465 (Triple-Bead Mixed Amphetamine Salts) for the Treatment of ADHD in Adults

May 19, 2007, 01:00 ET from Shire plc

    BASINGSTOKE, United Kingdom, and PHILADELPHIA, May 19 /PRNewswire/ --
 Shire plc (LSE: SHP; Nasdaq:   SHPGY; TSX: SHQ) announced today that it has
 received an approvable letter from the U.S. Food and Drug Administration
 (FDA) for SPD465 (triple-bead mixed amphetamine salts [MAS], an
 investigational oral stimulant intended to provide symptom control of ADHD
 in adults for up to 16 hours with one daily dose. Following receipt of this
 approvable letter, Shire is evaluating its options related to SPD465.
     Shire submitted a New Drug Application for SPD465 on July 21, 2006.(1)
 If approved, SPD465 will be a treatment option for adults with ADHD and
 part of Shire's overall ADHD portfolio.
     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 in their lives, according to the CDC.(2) ADHD is one of the most
 common psychiatric disorders in children and adolescents.(3) The disorder
 is also estimated to affect approximately 9.8 million adults across the
 U.S. based on a retrospective survey of adults aged 18 to 34, projected to
 the full U.S. adult population.(4,5) ADHD is a neurobiological psychiatric
 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.(6)
 To be properly diagnosed with ADHD, a child needs to demonstrate at least
 six of nine symptoms of inattention; and/or at least six of nine symptoms
 of hyperactivity/impulsivity; the onset of which appears before age 7
 years; that some impairment from the symptoms is present in two or more
 settings (e.g., at school and home); that the symptoms continue for at
 least six months; and that there is clinically significant impairment in
 social, academic or occupational functioning and the symptoms cannot be
 better explained by another psychiatric disorder.(6)
     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.(7)
     For further information on ADHD please visit www.adhdsupport.com.
     Shire ADHD Portfolio
     In addition to SPD465, Shire's portfolio of ADHD treatments includes
 VYVANSE(TM) (lisdexamfetamine dimesylate), the first prodrug stimulant,
 which is planned to launch 2Q 2007, DAYTRANA(TM) (methylphenidate
 transdermal system), the first and only ADHD patch, and ADDERALL XR(R)
 (mixed salts of a single-entity amphetamine product), a long-acting
 formulated stimulant. SPD503 (guanfacine HCl extended release) is currently
 under review with FDA.
     About SPD465
     SPD465, a single entity formulation of mixed amphetamine salts, was
 designed to provide extended release of medication with symptom control for
 up to 16 hours, is being studied for the treatment of ADHD in adults. The
 most common adverse events reported include insomnia, decreased appetite,
 dry mouth, headache and weight decrease.
     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
     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 - 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 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.
     About DAYTRANA
     DAYTRANA should not be used in patients with allergy to methylphenidate
 or patch components; marked anxiety, tension and agitation; glaucoma; tics,
 diagnosis or a family history of Tourette's syndrome; seizures; or during
 or within 14 days after treatment with monoamine oxidase inhibitors
     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 deaths,
 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; EEG abnormalities;
 bipolar disorder; depression. Growth and hematologic monitoring is advised
 during prolonged treatment. Patients should avoid applying external heat to
 the DAYTRANA patch. Skin irritation or contact sensitization may occur.
     DAYTRANA should be given cautiously to patients with a history of drug
 dependence and alcoholism. Chronic abuse can lead to marked tolerance and
 psychological dependence. Frank psychotic episodes can occur, especially
 with parenteral abuse. Careful supervision is required during withdrawal
     abusive use, since severe depression may occur. Withdrawal following
 chronic therapeutic use may unmask symptoms of the underlying disorder.
     Common adverse events reported by patients who received DAYTRANA in
 clinical trials were decreased appetite, insomnia, nausea, vomiting,
 decreased weight, tics, affect lability, and anorexia, consistent with
 adverse events commonly associated with the use of methylphenidate.
     For further product information related to Shire's portfolio of ADHD
 treatments, please go to Vyvanse.com, AdderallXR.com and Daytrana.com.
     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 and
 hyperactivity disorder (ADHD), human genetic therapies (HGT),
 gastrointestinal (GI) and renal diseases. The structure is sufficiently
 flexible to allow Shire to target new therapeutic areas to the extent
 opportunities arise through acquisitions. Shire believes that a carefully
 selected portfolio of products with a strategically aligned 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:
 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, Shire's results could be
 materially affected. The risks 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 Deficit and
 Hyperactivity Disorder ("ADHD") franchise; patents, including but not
 limited to, legal challenges relating to Shire's ADHD franchise; government
 regulation and approval, including but not limited to the expected product
 approval dates of SPD503 (guanfacine extended release) (ADHD) and SPD465
 (extended release triple-bead mixed amphetamine salts) (ADHD); Shire's
 ability to secure new products for commercialization and/or development;
 Shire's ability to benefit from its acquisition of New River
 Pharmaceuticals Inc.; and other risks and uncertainties detailed from time
 to time in Shire plc's filings with the Securities and Exchange Commission,
 particularly Shire plc's Annual Report on Form 10-K for the year ended
 December 31, 2006.
     (1) Shire Pharmaceuticals Group. Basingstoke: Shire; [updated 2006 Oct.
 20; cited 2006 Oct. 19]. Shire Announces Filing Of Spd465 For The Treatment
 Of Adult ADHD. Available from
     (2) Mental health in the United States: Prevalence of diagnosis and
 medication treatment 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
 Hyperactivity Disorder. 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 on
 June 8, 2005.
     (4) Kessler RC, et al. "The Prevalence and Correlates of Adult ADHD in
 the United States: Results from the National Comorbidity Survey
 Replication." The American Journal of Psychiatry. 2006;163:716-723., US
 Census 2005. Data
     extrapolated from survey data in adults 18-44 years old, projected to
 the total adult population in the US.
     (5) "Annual Estimates of the Population by Selected Age Groups and Sex
 for the United States: April 1, 2000 to July 1, 2005 (NC-EST2005-02)." U.S.
 Census Bureau. Available at:
 http://www.census.gov/popest/national/asrh/NC-EST2005-sa.html. Accessed May
 7, 2007.
     (6) Diagnostic and Statistical Manual of Mental Disorders: Fourth
 Edition, Text Revision. DSM-TR-IV(R). Washington, DC: American Psychiatric
 Association; 2000: 85.
     (7) Baumgartel A, et al. Practice guideline for the diagnosis and
 management of attention deficit hyperactivity disorder. Ambulatory Child
 Health. 1998;4:51.

SOURCE Shire plc