Vyvanse@ (lisdexamfetamine dimesylate) Capsules, (CII) Now Approved in

the US for Maintenance Treatment in Adults with ADHD

PHILADELPHIA, Feb. 7, 2012 /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 for adults with ADHD. The

approval is based on results from a randomized withdrawal study

designed to evaluate the efficacy of Vyvanse in adults (aged 18 to 55

years) who were receiving treatment with Vyvanse for a minimum of 6

months prior to enrolling in the study. Significantly more patients

treated with Vyvanse maintained ADHD symptom control compared with

placebo as determined by the proportion of patients who met criteria

for relapse of symptoms at end point during the six-week randomized

double-blind withdrawal phase of the study (8.9% of Vyvanse-treated

patients vs 75% for placebo). This new approval adds to the

indication for Vyvanse as a treatment for ADHD in patients ages 6 and


Vyvanse should be used as part of a total treatment program that may

include counseling or other therapies. The physician who elects to use

Vyvanse for extended periods should periodically reevaluate the

long-term usefulness of the drug for the individual patient.

In a randomized withdrawal design, patients who respond to a treatment

are randomized to continue receiving that treatment or placebo.

Utilizing 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. "Data from this

study and the resulting approval illustrate that Vyvanse can help

adults with ADHD maintain symptom control. Vyvanse is the first

medicine both proven to work and approved to maintain efficacy in

adults with ADHD," said Jeffrey Jonas, MD, Senior Vice President of

Research and Development for Shire's Specialty Pharmaceuticals and

Regenerative Medicine businesses. "This underscores Shire's commitment

to providing important advances in the treatment of individuals with

ADHD by investing in innovative research in this area," added Dr.


Vyvanse is a Schedule II controlled substance. Stimulants, such as

amphetamines and methylphenidates, are subject to misuse, abuse,

addiction, and criminal diversion. Misuse of amphetamines may cause

sudden death and serious cardiovascular adverse events.

This Phase 4, double-blind, multi-center, placebo-controlled,

randomized withdrawal design study assessed the maintenance of

efficacy and safety of Vyvanse in 123 adults who met DSM-IV-TR@

criteria for ADHD. Prior to enrollment, patients were required to have

documented long-term treatment with Vyvanse (30, 50, or 70 mg/day) for

at least 6 months and demonstrated treatment response as defined by an

ADHD Rating Scale IV (ADHD-RS-IV) with adult prompts total score of

<22 and Clinical Global Impressions-Severity (CGI-S) ratings less than

or equal to 3. After screening, eligible patients entered a three-week

open-label treatment phase in which they continued to receive the same

Vyvanse dose they were taking at study entry. Following this

open-label treatment, patients who maintained treatment response at

week 3 entered the six-week double-blind, randomized withdrawal phase

(n116), in which they received on-going treatment with the same dose

of Vyvanse (n56), or switched to placebo (n60). The ADHD-RS-IV with

adult prompts is a clinician assessment of the severity of the core

symptoms of ADHD. The CGI-S is a clinician assessment of symptom


The primary efficacy outcome measure was the proportion of patients

who met criteria for relapse of ADHD symptoms at end point during the

double-blind, randomized withdrawal phase. End point was defined as

the last post-randomization treatment week at which a valid ADHD-RS

with adult prompts total score and CGI-S were observed. Relapse of

ADHD symptoms was defined as a greater than or equal to 50% increase

(worsening) in the ADHD-RS-IV with adult prompts total score and a

greater than or equal to 2-point increase in the CGI-S score compared

to scores at entry into the double-blind randomized withdrawal phase.

Patients who met criteria for relapse of ADHD symptoms were

immediately discontinued from the study.

On the primary efficacy measure, significantly fewer patients met

criteria for symptom relapse with Vyvanse (8.9 versus placebo (75%)

(P<.0001) at end point of the randomized withdrawal phase. The

majority (approximately 62 of placebo treated patients who met

criteria for relapse of ADHD symptoms did so within 2 weeks following


During the open-label phase, seven patients discontinued from the

study, including one patient on Vyvanse who discontinued due to a

treatment-emergent adverse event (TEAE) (lack of efficacy). One

serious adverse event (SAE) was reported during the randomized

withdrawal phase in a patient receiving placebo (suicidal ideation).

No SAEs were reported in patients receiving Vyvanse, and no deaths

were reported. During the randomized withdrawal phase, 48.2% (27/56)

of patients receiving Vyvanse and 30% (18/60) on placebo reported

TEAEs. The most common (greater than or equal to 2 TEAEs reported in

the Vyvanse treatment group included headache, upper respiratory tract

infection, insomnia, fatigue and joint sprain. Mean systolic and

diastolic blood pressure and pulse rate were slightly higher for

Vyvanse-treated patients compared to placebo-treated patients. Small

changes in mean blood pressure and pulse rate were observed from

baseline to week 3 in the open-label phase and at end point of the

randomized withdrawal phase for both Vyvanse and placebo treatment

groups. The safety profile seen in this study was consistent with that

of other studies of Vyvanse. No new clinically relevant safety signals

were associated with abrupt discontinuation of Vyvanse.

"The finding from this study is important because adult patients with

ADHD may have a need for extended treatment, and could benefit from a

treatment option proven to maintain efficacy," stated Matthew Brams,

MD, Principal Investigator and Clinical Assistant Professor of

Psychiatry at Baylor College of Medicine. "This study showed that in

patients with ADHD who were stable on Vyvanse for 6 months, 91%

randomized to receive Vyvanse continued to maintain symptom control

compared with 25% taking placebo."

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, and approved in November 2010 to

treat ADHD in adolescents ages 13 to 17, is currently available in six

once-daily dosage strengths of 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, and

70 mg.

Additional information about Vyvanse is available at


Vyvanse is indicated for the treatment of ADHD in patients ages 6 and

above as part of a total treatment plan that may include other

measures (psychological, educational, social). Efficacy was

established in short-term controlled studies in children aged 6 to 17

and adults. Vyvanse is also approved as a maintenance treatment for

adults with ADHD based on one randomized withdrawal study. Extended

use of Vyvanse should be periodically reevaluated to determine its

long-term usefulness for the individual patient.




Full Prescribing Information for complete Boxed WARNING.

-- Vyvanse is a Schedule II controlled substance. Stimulants, such as

amphetamines and methylphenidates, are subject to misuse, abuse,

addiction, and criminal diversion.

-- Misuse of amphetamines may cause sudden death and serious

cardiovascular adverse events.


-- Contraindications: Known hypersensitivity to amphetamines or other

ingredients in Vyvanse. Anaphylactic reactions, Stevens-Johnson

Syndrome, angioedema, and urticaria have been observed in

postmarketing reports. Using Vyvanse with monoamine oxidase inhibitors

(MAOIs) can result in hypertensive crisis. Stop MAOIs at least 14 days

prior to Vyvanse use.

-- Sudden death, stroke and myocardial infarction have been reported

with stimulants at usual doses for the treatment of ADHD. Stimulants

generally should not be used in patients with known structural

cardiac abnormalities or other serious heart problems. Adults have a

greater likelihood than children of having such cardiac disease.

Patients being considered for stimulant treatment should have a

careful history (including family history of sudden death or

ventricular arrhythmia) and physical exam to assess for the presence

of cardiac disease. Further evaluation should be conducted if needed

(eg, electrocardiogram and echocardiogram). Patients who develop

symptoms suggestive of cardiac disease (eg, exertional chest pain,

unexplained syncope) during stimulant treatment should undergo a

prompt evaluation.

-- Use with caution in patients whose underlying medical condition

might be compromised by increases in blood pressure or heart rate.

Stimulants cause modest increases in average blood pressure (about 2-4

mmHg) and average heart rate (about 3-6 bpm) and patients may have

larger increases. Monitor all patients for larger changes.

-- Use of stimulants may cause psychotic or manic symptoms in patients

with no prior history, or exacerbation of symptoms in patients with

pre-existing psychosis. Clinical evaluation for bipolar disorder is

recommended prior to stimulant use. Monitor for aggressive behavior.

-- Monitor growth in children during treatment with Vyvanse. Children

who are not growing (gaining height or weight) as expected may need to

have their treatment interrupted.

-- Stimulants may lower the convulsive threshold. Discontinue if

seizures develop.

-- Visual disturbances and exacerbation of tics and Tourette's

syndrome have been reported with stimulant treatment.

-- The most common adverse reactions (greater than or equal to 5% and

at least twice the rate of placebo) reported in clinical trials were:

Children aged 6 to 12:decreased appetite, insomnia, upper abdominal

pain, irritability, decreased weight, vomiting, nausea, dizziness and

dry mouth; Adolescents aged 13 to 17: decreased appetite, insomnia,

and decreased weight; Adults: decreased appetite, insomnia, dry mouth,

nausea, diarrhea, anxiety and anorexia.

Please click here for Full Prescribing Information for Vyvanse

(lisdexamfetamine dimesylate), including Boxed WARNING regarding

Potential for Misuse, Abuse, Addiction, and Diversion .

ABOUT ADHD Attention-Deficit/Hyperactivity Disorder is a

neurobehavioral disorder that manifests as a persistent pattern of

inattention and/or hyperactivity-impulsivity and 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.

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 Mental Disorders, 4th Edition, Text Revision

(DSM-IV-TR@) or International Classification of Diseases, 10th


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.

For further information please contact:

Investor Relations

Eric Rojas +1 781 482 0999

Sarah Elton-Farr +44 1256 894157


Jessica Mann (Corporate) +44 1256 894 280

Gwen Fisher (Specialty Pharma) +1 484 595 9836

Notes to editors


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

hyperactivity disorder, human genetic therapies, gastrointestinal

diseases and regenerative medicine as well as opportunities in other

therapeutic areas to the extent they arise through acquisitions.

Shire's in-licensing, merger and acquisition efforts are focused on

products in specialist markets with strong intellectual property

protection and global rights. Shire believes that a carefully

selected and balanced portfolio of products with strategically aligned

and relatively small-scale sales forces will deliver strong results.

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, the

Company's results could be materially adversely affected. The risks

and uncertainties include, but are not limited to, risks associated

with: the inherent uncertainty of research, development, approval,

reimbursement, manufacturing and commercialization of the Company's

Specialty Pharmaceuticals, Human Genetic Therapies and Regenerative

Medicine products, as well as the ability to secure new products for

commercialization and/or development; government regulation of the

Company's products; the Company's ability to manufacture its products

in sufficient quantities to meet demand; the impact of competitive

therapies on the Company's products; the Company's ability to

register, maintain and enforce patents and other intellectual property

rights relating to its products; the Company's ability to obtain and

maintain government and other third-party reimbursement for its

products; and other risks and uncertainties detailed from time to time

in the Company's filings with the Securities and Exchange Commission.

SOURCE Shire plc

-0- 02/07/2012

/Web Site:



CO: Shire plc

ST: Pennsylvania




-- NY48957 --

0000 02/07/2012 17:37:13 EDT