Vyvanse® (lisdexamfetamine dimesylate) Capsules, (CII) Now Approved in the US for Maintenance Treatment in Children and

Vyvanse® (lisdexamfetamine dimesylate) Capsules, (CII) Now Approved in the US
       for Maintenance Treatment in Children and Adolescents with ADHD

Becomes the first stimulant medication approved for maintenance treatment in
patients ages 6 and above with ADHD

PR Newswire


PHILADELPHIA, May 1, 2013 /PRNewswire/ --

Shire plc (LSE: SHP, NASDAQ: SHPGY), the global specialty biopharmaceutical
company, today announced that the US Food and Drug Administration (FDA)
approved the prescription medication Vyvanse^® (lisdexamfetamine dimesylate)
Capsules, (CII) as a maintenance treatment in children and adolescents with
Attention-Deficit/Hyperactivity Disorder (ADHD). Vyvanse is currently approved
as a maintenance treatment in adults with ADHD. With this new approval,
Vyvanse becomes the only stimulant approved for maintenance treatment in
children, adolescents, and adults (patients ages 6 and above) with ADHD.

The approval is based on results from a 32-week study: 26 weeks of open-label
treatment with Vyvanse followed by a 6-week randomized withdrawal phase. The
study was designed to evaluate the continued efficacy of Vyvanse in children
and adolescents (aged 6 to 17 years). A significantly lower proportion of
treatment failures occurred among Vyvanse patients (15.8%) compared to placebo
(67.5%) at end point of the randomized withdrawal period, showing that
significantly more patients treated with Vyvanse maintained ADHD symptom
control compared with placebo.

"It's important to help establish and maintain effective control of symptoms
in patients with ADHD," said Valerie Arnold, MD, an investigator in the
randomized withdrawal study. "With this study, physicians now have clinical
data in children and adolescents ages 6 and above showing the effectiveness of
Vyvanse as a maintenance treatment for ADHD. This additional approval of
Vyvanse is welcome because children and adolescents with ADHD may have a need
for extended treatment, and could benefit from a treatment option proven to
maintain efficacy."

Vyvanse is a Schedule II controlled substance. CNS Stimulants (amphetamines
and methylphenidate-containing products) have a high potential for abuse and
dependence. Assess the risk of abuse prior to prescribing and monitor for
signs of abuse and dependence.

To evaluate the efficacy of Vyvanse for maintenance treatment in children and
adolescents with ADHD, Shire elected to conduct a double-blind,
placebo-controlled, randomized withdrawal clinical trial. In this design,
patients who respond to a treatment are randomized to continue receiving that
treatment or placebo. Using the proportion of patients experiencing symptom
relapse as a primary outcome, this type of study in patients with ADHD can be
used to demonstrate long-term efficacy in lieu of conducting a long-term,
placebo-controlled, parallel-group study. The utility of this design is that
the period of placebo exposure, with the potential for worsening of ADHD
symptoms, is relatively short.

The double-blind, placebo-controlled, randomized withdrawal study was
conducted in 276 children and adolescents aged 6 to 17 with ADHD. Of these
patients, 236 participated in a preceding study and 40 directly enrolled. The
study consisted of 4 phases:

  o4-week, open-label, dose-optimization phase in which patients received
    Vyvanse 30 mg/day, 50 mg/day, or 70 mg/day. Eligible subjects started on
    Vyvanse 30 mg/day and could be titrated in weekly increments of 20 mg
    until an optimal dose was reached (up to a maximum of 70 mg/day)
  o20-week, open-label, maintenance phase
  o2-week, open-label, fixed-dose phase in which patients were discontinued
    if they required further dose adjustments, experienced unacceptable
    tolerability, or had an Attention-Deficit/Hyperactivity Disorder Rating
    Scale, Version IV (ADHD-RS-IV) total score >22 or Clinical Global
    Impression Severity (CGI-S) score ≥3. Patients who maintained treatment
    response entered the randomized withdrawal phase.
  o6-week, double-blind, randomized withdrawal phase in which patients either
    received ongoing treatment with the same dose of Vyvanse (N=78) or were
    switched to placebo (N=79).

The primary outcome measure was the proportion of patients who met criteria
for relapse of ADHD symptoms (treatment failure) at end point during the
double-blind, randomized withdrawal phase. The end point measurement was
defined as the last post-randomization treatment week at which a valid ADHD-RS
Total Score and CGI-S were observed. Treatment failure was defined as a ≥50%
increase (worsening) in the ADHD-RS Total Score and a ≥2-point increase in the
CGI-S score compared to scores at entry into the double-blind, randomized
withdrawal phase. On the primary end point, significantly fewer patients met
criteria for symptom relapse with Vyvanse (15.8%) versus placebo (67.5%)

During the 26-week open-label phase, 12 patients (4.3%) reported serious
adverse events (SAEs), and 45 patients (16.3%) reported treatment-emergent
adverse events (TEAEs) that resulted in Vyvanse discontinuation. During the
randomized withdrawal phase, no SAEs were reported in the Vyvanse group, no
patients in the Vyvanse group discontinued due to a TEAE, and 1 patient in the
placebo group discontinued due to a TEAE. In addition, 39.7% (31/78) of
patients receiving Vyvanse and 25.3% (20/79) on placebo reported TEAEs. The
most common TEAEs (≥2%) reported in the Vyvanse treatment group during the
randomized withdrawal phase included nasopharyngitis, headache, abdominal pain
upper, oropharyngeal pain, decreased appetite, vomiting, weight decrease,
abdominal pain, accidental overdose, aggression, cough, nausea and rhinitis.

Patients receiving Vyvanse demonstrated a moderate increase in mean pulse rate
(~5 beats per minute) and blood pressure (~2 mm Hg systolic and diastolic
blood pressure) between baseline and end point of the randomized withdrawal
period. Patients treated with Vyvanse experienced a mean decrease in body
weight of about 2 kg during the 26-week open-label period. Mean weight tended
to increase in patients who switched to placebo during the randomized
withdrawal phase. There were no deaths reported during the trial. The safety
profile seen in this study was consistent with that of other studies of
Vyvanse, and no new clinically relevant safety signals were associated with
abrupt discontinuation of Vyvanse.

"This study is evidence of Shire's commitment to conducting research in ADHD
and contributing to the body of knowledge about treatment options," said
Arnaud Partiot, M.D., Ph.D., senior vice president and head of Research and
Development for Shire. "Vyvanse is now the only stimulant approved for
maintenance treatment in patients ages 6 and above."

ABOUT VYVANSE (lisdexamfetamine dimesylate)

Vyvanse, which was introduced in the United States in July 2007 for the
treatment of ADHD in children ages 6 to 12 years, approved in April 2008 to
treat ADHD in adults, approved in November 2010 to treat ADHD in adolescents
ages 13 to 17, approved in January 2012 for maintenance treatment in adults,
and approved in April 2013 for maintenance treatment in children and
adolescents, is currently available in six once-daily dosage strengths of 20
mg, 30 mg, 40 mg, 50 mg, 60 mg, and 70 mg.

Vyvanse may be used as part of a total treatment program that may include
counseling or other therapies.

Additional information about Vyvanse is available at http://www.vyvanse.com.


Vyvanse is indicated for the treatment of Attention Deficit Hyperactivity
Disorder (ADHD).

The efficacy of Vyvanse in the treatment of ADHD was established on the basis
of three short-term controlled trials in children ages 6 to 12 years, one
short-term controlled trial in adolescents ages 13 to 17 years, one short-term
trial in children and adolescents ages 6-17 years, one maintenance trial in
children and adolescents ages 6-17 years, two short-term controlled trials in
adults, and one maintenance trial in adults.



       oKnown hypersensitivity to amphetamines or other ingredients in
         Vyvanse. Anaphylactic reactions, Stevens - Johnson syndrome,
         angioedema, and urticaria have been observed in postmarketing
       oConcurrent administration of monoamine oxidase inhibitors (MAOI) or
         administration of Vyvanse within 14 days of the last MAOI dose.
         Hypertensive crisis can occur.

  oEducate patients about abuse and periodically re-evaluate the need for
  oSudden death, stroke and myocardial infarction have been reported in
    adults with CNS stimulant treatment at recommended doses. Sudden death has
    been reported in children and adolescents with structural cardiac
    abnormalities and other serious heart problems taking CNS stimulants at
    recommended doses for ADHD. Prior to treatment assess for the presence of
    cardiac disease. Avoid use in patients with known structural cardiac
    abnormalities, cardiomyopathy, serious heart arrhythmia, coronary artery
    disease, and other serious heart problems. Further evaluate patients who
    develop exertional chest pain, unexplained syncope, or arrhythmias during
    Vyvanse treatment.
  oCNS stimulants cause an increase in blood pressure (mean increase about
    2-4 mm Hg) and heart rate (mean increase about 3-6 bpm). Monitor all
    patients for tachycardia and hypertension.
  oUse of stimulants may cause psychotic or manic symptoms in patients with
    no prior history, or exacerbation of symptoms in patients with preexisting
    psychosis. Clinical evaluation for bipolar disorder is recommended prior
    to stimulant use.
  oCNS stimulants have been associated with weight loss and slowing of growth
    rate in pediatric patients. Monitor weight and height in children during
    treatment with Vyvanse. Treatment may need to be interrupted in children
    not growing as expected.
  oThe most common adverse reactions (≥5% and at least twice the rate of
    placebo) reported in clinical trials were:  

       oChildren aged 6 to 12: decreased appetite, insomnia, upper abdominal
         pain, irritability, vomiting, decreased weight, nausea, dry mouth and
       oAdolescents aged 13 to 17: decreased appetite, insomnia, and
         decreased weight;
       oAdults: decreased appetite, insomnia, dry mouth, diarrhea, nausea,
         anxiety and anorexia.

Please click here forFull Prescribing Information.


Attention-Deficit/Hyperactivity Disorder is a neurobehavioral 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.

ADHD is one of the most common childhood psychiatric disorders. Although many
people tend to think of ADHD as a childhood problem, 60% to 85% of children
with ADHD may continue to meet the criteria for the disorder during their
teenage years. Nearly 50% of children with ADHD may continue to meet the
criteria for the disorder into adulthood, based on parent-report. The disorder
is 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, approximately 10
million adults are estimated to have ADHD. Drug treatment may not be
appropriate for all patients.

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 specified in the Diagnostic and Statistical Manual of
MentalDisorders, 4th Edition, Text Revision (DSM-IV-TR®) or International
Classification of Diseases, 10^th revision (ICD-10).

Although there is no cure for ADHD, there are accepted treatments that have
been demonstrated to improve symptoms. Standard treatments include educational
approaches, psychological therapies which may include behavioral modification,
and/or medication. Ongoing assessment and treatment may be necessary.


Shire enables people with life-altering conditions to lead better lives.

Through our deep understanding of patients' needs, we develop and provide
healthcare in the areas of:

  oBehavioral Health and Gastrointestinal conditions
  oRare Diseases
  oRegenerative Medicine

as well as other symptomatic conditions treated by specialist physicians.

We aspire to imagine and lead the future of healthcare, creating value for
patients, physicians, policymakers, payors and our shareholders.



Statements included in this announcement that are not historical facts are
forward-looking statements. 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
adversely affected. The risks and uncertainties include, but are not limited
to, that:

  oShire's products may not be a commercial success;
  orevenues from ADDERALL XR are subject to generic erosion;
  othe failure to obtain and maintain reimbursement, or an adequate level of
    reimbursement, by third-party payors in a timely manner for Shire's
    products may impact future revenues and earnings;
  oShire relies on a single source for manufacture of certain of its products
    and a disruption to the supply chain for those products may result in
    Shire being unable to continue marketing or developing a product or may
    result in Shire being unable to do so on a commercially viable basis;
  oShire uses third party manufacturers to manufacture many of its products
    and is reliant upon third party contractors for certain goods and
    services, and any inability of these third party manufacturers to
    manufacture products, or any failure of these third party contractors to
    provide these goods and services, in each case in accordance with its
    respective contractual obligations, could adversely affect Shire's ability
    to manage its manufacturing processes or to operate its business;
  othe development, approval and manufacturing of Shire's products is subject
    to extensive oversight by various regulatory agencies and regulatory
    approvals or interventions associated with changes to manufacturing sites,
    ingredients or manufacturing processes could lead to significant delays,
    increase in operating costs, lost product sales, an interruption of
    research activities or the delay of new product launches;
  othe actions of certain customers could affect Shire 's ability to sell or
    market products profitably and fluctuations in buying or distribution
    patterns by such customers could adversely impact Shire's revenues,
    financial conditions or results of operations;
  oinvestigations or enforcement action by regulatory authorities or law
    enforcement agencies relating to Shire's activities in the highly
    regulated markets in which it operates may result in the distraction of
    senior management, significant legal costs and the payment of substantial
    compensation or fines;
  oadverse outcomes in legal matters and other disputes, including Shire's
    ability to obtain, maintain, enforce and defend patents and other
    intellectual property rights required for its business, could have a
    material adverse effect on Shire's revenues, financial condition or
    results of operations;
  oand other risks and uncertainties detailed from time to time in Shire's
    filings with the U.S. Securities and Exchange Commission, including its
    most recent Annual Report on Form 10-K.

VYV-05105 04/13

Vyvanse® is a registered trademark of Shire LLC.

For further information please contact:

Investor Relations   

Eric Rojas

Sarah Elton-Farr


Jessica Mann (Corporate)

Gwen Fisher (Specialty Pharma)

SOURCE Shire plc
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