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:
- 4-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)
- 20-week, open-label, maintenance phase
- 2-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.
- 6-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%) (P<.001).
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.
INDICATION
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.
IMPORTANT SAFETY INFORMATION
- Contraindications:
- Known hypersensitivity to amphetamines or other ingredients in
Vyvanse. Anaphylactic reactions, Stevens - Johnson syndrome, angioedema, and
urticaria have been observed in postmarketing reports.
- Concurrent administration of monoamine oxidase inhibitors
(MAOI) or administration of Vyvanse within 14 days of the last MAOI
dose. Hypertensive crisis can occur.
- Educate patients about abuse and periodically re-evaluate the
need for Vyvanse.
- Sudden 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.
- CNS 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.
- Use 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.
- CNS 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.
- The most common adverse reactions (≥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, vomiting, decreased weight,
nausea, dry mouth and dizziness;
- Adolescents aged 13 to 17: decreased appetite, insomnia,
and decreased weight;
- Adults: decreased appetite, insomnia, dry mouth,
diarrhea, nausea, anxiety and anorexia.
Please click here for Full Prescribing
Information.
ABOUT ADHD
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, 10th 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.
NOTES TO EDITORS
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:
- Behavioral Health and Gastrointestinal conditions
- Rare Diseases
- Regenerative 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.
http://www.shire.com
FORWARD - LOOKING STATEMENTS - "SAFE
HARBOR" STATEMENT UNDER THE PRIVATE SECURITIES LITIGATION REFORM
ACT OF 1995
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:
- Shire's products may not be a commercial success;
- revenues from ADDERALL XR are subject to generic erosion;
- the 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;
- Shire 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;
- Shire 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;
- the 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;
- the 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;
- investigations 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;
- adverse 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;
- and 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
erojas@shire.com
+1-781-482-0999
Sarah Elton-Farr
seltonfarr@shire.com
+44-(0)1256-894157
Media
Jessica Mann (Corporate)
jmann@shire.com
+44-(0)1256-894-280
Gwen Fisher (Specialty
Pharma)
gfisher@shire.com
+1-484-595-9836
SOURCE Shire plc