U.S. FDA Approves
MydayisTM (mixed salts of a single-entity amphetamine
product) – A New Once-Daily Option for ADHD Symptom Control in
Patients 13 Years and Older
Mydayis
demonstrated improvements lasting up to 16 hours post-dose,
beginning at 2 or 4 hours post-administration, compared to placebo,
in total score on a skill-adjusted math test that measures
attention in ADHD
Lexington, Mass., USA –
June 20, 2017 – Shire plc
(LSE: SHP, NASDAQ: SHPG) announced today that the U.S. Food and
Drug Administration (FDA) has approved MYDAYISTM (mixed
salts of a single-entity amphetamine product), a once-daily
treatment comprised of three different types of drug-releasing
beads for patients 13 years and older with Attention Deficit
Hyperactivity Disorder (ADHD). Mydayis is not for use in children
12 years and younger. Shire expects to make Mydayis commercially
available in the United States in
the third quarter of 2017.
The U.S. FDA approval of Mydayis is based on results from 16
clinical studies evaluating Mydayis in more than 1,600 subjects,
including adolescents (aged 13 to 17 years) and adults with ADHD.
In pivotal, placebo-controlled clinical studies, Mydayis
significantly improved symptoms of ADHD, as measured by the
ADHD-RS-IV and the Permanent Product Measure of Performance
(PERMP), in adults and adolescents. Improvement on the PERMP, an
objective, validated, skill-adjusted math test that measures
attention in ADHD patients, reached statistical significance
beginning at 2 or 4 hours post-dose and lasting up to 16 hours
post-dose.
“Mydayis is the latest innovation in Shire’s 20-year legacy of
helping to support the treatment of ADHD. It’s a testament to
Shire’s commitment to helping support the evolving needs of
appropriate patients with ADHD,” said Flemming Ornskov, M.D., MPH,
CEO of Shire. “With this approval, we hope to help patients who
need a once-daily treatment option. Mydayis has shown efficacy
lasting up to 16 hours after taking one capsule, beginning at 2 or
4 hours post-dose.”
Andrew J. Cutler, M.D., Executive
Vice President and Chief Medical Officer at Meridien Research and
an investigator in the Mydayis clinical trials said: “Many of my
patients living with ADHD are trying to manage symptoms that impact
them in different settings – often across home life, school or
work, and in social settings. Patients have individual needs and
may respond differently to treatments, so it is important for
healthcare professionals to have multiple options. It’s rewarding
to work with Shire to provide a new treatment option that may help
appropriate patients with ADHD.”
Mydayis, other amphetamine containing
medicines, and methylphenidate have a high chance for abuse and can
cause physical and psychological dependence. Your healthcare
provider should check you or your child for signs of abuse and
dependence before and during treatment with Mydayis.
In pivotal Phase 3 clinical studies where efficacy was the
primary endpoint, a morning dose of Mydayis demonstrated
superiority to placebo based on the change from baseline in the
ADHD-RS-IV total score for adult and adolescent patients,
respectively. The most common adverse reactions associated with
Mydayis (incidence ?5% and at a rate at least twice placebo) in
adults are insomnia, decreased appetite, decreased weight, dry
mouth, increased heart rate, and anxiety. For pediatric patients
(13 years and older), the most common adverse reactions were
insomnia, decreased appetite, decreased weight, irritability, and
nausea.
In Phase 2 studies (two studies in adults and one in
adolescents), patients treated with Mydayis demonstrated improved
attention compared to placebo, as assessed by the total PERMP
score, with results reaching statistical significance beginning at
2 or 4 hours post-dose, and lasting up to 16 hours post-dose.
Across all clinical studies, adverse events were generally mild to
moderate in severity and similar to those observed with other
amphetamine compounds.
ADHD is a neurodevelopmental disorder that manifests as a
persistent pattern of inattention and/or hyperactivity-impulsivity
that interferes with functioning or development. An estimated 4.4%
of adults have ADHD in the U.S. When applied to the full U.S. adult
population aged 18 and over, approximately 10.5 million adults are
estimated to have ADHD in the U.S. Approximately 50 to 66% of
children with ADHD may continue to have ADHD symptoms as adults.
Medication is not appropriate for all individuals diagnosed with
ADHD.
“Being diagnosed with ADHD as an adult helped me understand my
symptoms,” said Gina D’Angelo, an adult patient with ADHD. “Living
with my ADHD symptoms is an ongoing process, and how I navigate my
daily responsibilities with ADHD changes as I learn more about it.
It is encouraging to see new options that may help adults manage
their ADHD symptoms.”
Mydayis (mixed salts of a single-entity amphetamine
product) Important Safety Information
What is MYDAYISTM?
Mydayis is a prescription medicine used for the treatment of
Attention Deficit Hyperactivity Disorder (ADHD) in patients 13
years and older. Mydayis is not for use in children 12 years and
younger.
IMPORTANT SAFETY INFORMATION
Abuse and dependence. Mydayis, other amphetamine
containing medicines, and methylphenidate have a high chance for
abuse and can cause physical and psychological dependence. Your
healthcare provider should check you or your child for signs of
abuse and dependence before and during treatment with Mydayis.
- Tell your healthcare provider if you or your child have ever
abused or been dependent on alcohol, prescription medicines, or
street drugs.
- Your healthcare provider can tell you more about the
differences between physical and psychological dependence and drug
addiction.
Who should not take Mydayis?
Do not take Mydayis if you or your
child is:
- allergic to amphetamine or any of the ingredients in Mydayis.
See the end of the Medication Guide for a complete list of
ingredients in Mydayis.
- taking, or have taken within the past 14 days, a medicine used
to treat depression called a monoamine oxidase inhibitor
(MAOI).
Problems that can occur while taking
Mydayis. Tell your doctor:
- if you or your child have any heart problems, heart defects,
high blood pressure, or a family history of these problems. This is
important because sudden death has occurred in people with heart
problems or defects taking stimulant medicines, and sudden death,
stroke and heart attack have happened in adults taking stimulant
medicines. Your healthcare provider should check you or your child
carefully for heart problems before starting Mydayis. Since
increases in blood pressure and heart rate may occur, your
healthcare provider should regularly check these during treatment.
Call your healthcare provider or go to the nearest hospital
emergency room right away if you or your child has any signs of
heart problems such as chest pain, shortness of breath, or fainting
while taking Mydayis.
- if you or your child have mental (psychiatric) problems, or a
family history of suicide, bipolar illness, or depression. This is
important because new or worse behavior and thought problems or new
or worse bipolar illness may occur. New symptoms such as hearing
voices, seeing or believing things that are not real, or new manic
symptoms may occur. Call your healthcare provider right away if
you or your child have any new or worsening mental symptoms or
problems during treatment, especially hearing voices, seeing or
believing things that are not real, or new manic symptoms.
- if your child is having slowing of growth (height and weight);
Mydayis may cause this serious side effect. Your child should have
height and weight checked often while taking Mydayis. Your
healthcare provider may stop treatment if a problem is found during
these check-ups.
- if you or your child have circulation problems in fingers and
toes (peripheral vasculopathy, including Raynaud’s phenomenon).
Fingers or toes may feel numb, cool, painful, sensitive to
temperature and/or change color from pale, to blue, to red. Tell
your healthcare provider if you or your child have any numbness,
pain, skin color change, or sensitivity to temperature in fingers
or toes. Call your healthcare provider if you or your child have
any signs of unexplained wounds appearing on fingers or toes while
taking Mydayis.
- if you have a seizure. Your healthcare provider will stop
treatment.
- if you have symptoms of serotonin syndrome such as agitation,
hallucinations, coma, or other changes in mental status; problems
controlling your movements or muscle twitching; fast heartbeat;
sweating or fever; nausea, vomiting or diarrhea; or muscle
stiffness or tightness. Call your healthcare provider or go to the
nearest hospital emergency room if you have these symptoms.
Serotonin syndrome may happen when Mydayis is taken with certain
other medicines and may be life-threatening.
- if you or your child are pregnant or plan to become pregnant.
It is not known if Mydayis may harm your unborn baby.
- if you or your child are breastfeeding or plan to breastfeed.
You should not breastfeed while taking Mydayis. Mydayis passes into
breast milk.
What are possible side effects of
Mydayis?
The most common side effects of Mydayis include:
- trouble sleeping
- decreased appetite
- dry mouth
- increased heart rate
- anxiety
- nausea
- irritability
- weight loss
For additional safety information, click here for
Prescribing Information, including Medication Guide and
Warning about Abuse, and discuss with your doctor.
You are encouraged to report negative side effects of
prescription drugs to the FDA. Visit
www.fda.gov/medwatch, or call 1-800-FDA-1088.
NOTES TO EDITORS
Stephen Williams, Deputy Company
Secretary, is responsible for arranging the release of this
announcement.
Inside Information
This announcement contains inside information.
More About ADHD
Attention Deficit Hyperactivity Disorder (ADHD) impacts people
in multiple settings – even beyond work into daily tasks, at home
or in social settings.
The specific etiology of ADHD is unknown. The diagnosis is made
utilizing criteria specified in the Diagnostic and Statistical
Manual of Mental Disorders, Fifth Edition
(DSM-5®). Only a trained healthcare professional
can evaluate and diagnose ADHD.
Although there is no cure for ADHD, there are accepted
treatments that have demonstrated improvement in ADHD symptoms. A
comprehensive approach is often advised, which may include a
combination of medication, psychotherapy and educational
approaches. Ongoing assessment of ADHD management plans is
recommended.
About the Mydayis Phase 3 Studies
Efficacy of Mydayis in adults (aged 18-55 years) was evaluated
in a pivotal randomized, double-blind, placebo-controlled study of
Mydayis 12.5 mg or 37.5 mg in 275 adult patients (Study 1) who met
the DSM-5® criteria for ADHD. The primary
endpoint was defined as the change from baseline in the ADHD-RS-IV
with prompts total score compared to placebo. When administered as
a daily morning dose, Mydayis was superior compared to placebo for
both the 12.5 mg and 37.5 mg doses, respectively. In addition,
patients treated with either 12.5 mg or 37.5 mg of Mydayis also
showed significantly greater improvement compared to placebo on the
Clinical Global Impression of Improvement (CGI-I) score, a key
secondary endpoint.
In a pooled analysis of three Phase 3 clinical trials conducted
in 626 adult ADHD patients, the most commonly reported TEAEs
(reported in >5% of Mydayis-treated patients) were insomnia,
decreased appetite, dry mouth, decreased weight, increased heart
rate, and anxiety. Nine percent of Mydayis-treated patients
discontinued due to adverse reactions compared to 2% of
placebo-treated patients. The most frequent adverse reactions
leading to discontinuation (i.e., leading to discontinuation in at
least 1% of Mydayis-treated patients and at a rate at least twice
that of placebo) were insomnia (2%), increased blood pressure (2%),
decreased appetite (1%), and headache (1%).
The efficacy of Mydayis was further assessed in a study that
included 157 adolescent (13 to 17 years old) patients (Study 4).
This was a randomized, double-blind, placebo-controlled,
dose-optimization study of Mydayis in patients who met the
DSM-IV-TR® criteria for ADHD. Subjects were
titrated from a dose of 12.5 mg/day until an optimal dose was
reached (up to a maximum dose of 25 mg/day). The primary efficacy
endpoint was defined as the change from baseline in the ADHD-RS-IV
total score when compared to placebo. The primary efficacy analysis
demonstrated that Mydayis, administered as a daily morning dose,
was superior to placebo with respect to the change from baseline on
the ADHD-RS-IV total score. In
addition, Mydayis also showed significantly greater improvement on
the CGI-I score at Week 4, the key secondary endpoint in this
study.
Among adolescent patients in Study 4, the most commonly reported
TEAEs (reported in >5% of Mydayis-treated patients) were
decreased appetite, nausea, insomnia, irritability, and decreased
weight. Five percent of Mydayis-treated patients discontinued due
to adverse reactions compared to zero percent of placebo-treated
patients. The most frequent adverse reaction leading to
discontinuation (i.e., leading to discontinuation in at least 1% of
Mydayis-treated patients and at a rate at least twice that of
placebo) were dizziness, depression, upper abdominal pain, and
viral infection (all 1%). Safety and effectiveness of Mydayis have
not been established in pediatric patients ages 12 years and
younger.
About the Mydayis Phase 2 Studies
The efficacy of Mydayis in adults (aged 18-55 years) was also
evaluated in two workplace analog studies. These were multi-center,
randomized, double-blind, placebo-controlled, crossover studies in
adult patients that evaluated 50 mg (Study 2, N=86, 42 of whom were
treated with 50 mg) or 25 mg (Study 3, N=79, 76 of whom were
treated with 25 mg) of Mydayis who met DSM-IV-TR®
criteria for ADHD. Efficacy was assessed by the PERMP total score,
calculated as the sum of the number of math problems attempted plus
the number of math problems answered correctly. The PERMP was
administered at 2, 4, 8, 12, 14, and 16 hours post-dose. Mydayis
treatment reached statistical significance compared to placebo at
either 2 hours (Study 2) or 4 hours (Study 3) post-dose and lasting
up to 16 hours post-dose in both studies.
In Study 2, no patients in the Mydayis 50 mg treatment group
experienced a serious TEAE. The most commonly reported TEAEs
(reported in >5% of patients) in the Mydayis 50 mg treatment
group included fatigue, insomnia, anorexia, decreased appetite,
headache, dry mouth, hypertension. In Study 3, no patients
experienced a serious TEAE. Two patients reported
treatment-emergent adverse events (TEAEs) that led to study
discontinuation. The most commonly reported TEAEs (reported in
>5% of patients) in the Mydayis 25 mg treatment group were
insomnia, decreased appetite, dry mouth, headache, and
anorexia.
The efficacy of Mydayis in adolescents was also evaluated in a
classroom analog study (Study 5, 13 to 17 years, N=84 adolescents).
The study was a multi-center, randomized, double-blind,
placebo-controlled, crossover study of Mydayis 12.5 mg or 25
mg who met DSM-IV-TR® criteria for ADHD.
Efficacy was assessed using the PERMP which was administered at 2,
4, 8, 12, 14, and 16 hours post-dose. Mydayis treatment, compared
to placebo, resulted in a statistically significant treatment
effect compared with placebo, beginning at 2 hours and continued
for up to 16 hours post-dose. In Study 5, TEAEs that were more
common in the Mydayis treatment arms (i.e., frequency >5% in
either Mydayis treatment arm) were upper abdominal pain, dry mouth,
nausea, anorexia, decreased appetite, dizziness, headache,
insomnia, irritability, and dysmenorrhea. There were no reported
serious TEAEs and no TEAEs led to study discontinuation.
DSM-5 and DSM-IV-TR are registered trademarks of
the American Psychiatric Association.
About Mydayis
Mydayis is a once-daily treatment comprised of three different
types of drug-releasing beads for patients 13 years and older with
ADHD. Mydayis is not for use in children 12 years and younger.
Mydayis will be available in 12.5, 25, 37.5 and 50 mg capsules.
Visit www.mydayis.com for more information.
Shire’s Commitment to ADHD
Shire is a global leader in ADHD education and treatment. We
have more than 20 years of experience in providing treatments for
ADHD. We regularly share our expertise with physicians, patients,
care givers and policymakers in order to raise awareness and
broaden understanding of this condition. Learn more at
www.shire.com.
About Shire
Shire is the leading global biotechnology company focused on
serving people with rare diseases and other highly specialized
conditions. We strive to develop best-in-class products, many of
which are available in more than 100 countries, across core
therapeutic areas including Hematology, Immunology, Neuroscience,
Ophthalmics, Lysosomal Storage Disorders, Gastrointestinal /
Internal Medicine / Endocrine and Hereditary Angioedema; and a
growing franchise in Oncology.
Our employees come to work every day with a shared mission: to
develop and deliver breakthrough therapies for the hundreds of
millions of people in the world affected by rare diseases and other
high-need conditions, and who lack effective therapies to live
their lives to the fullest.
www.shire.com
For further information please
contact:
Investor Relations
Ian
Karp
ikarp@shire.com
+1 781 482 9018
Robert Coates rcoates@shire.com
+44 1256 894874
Media
Gwen Fisher
gfisher@shire.com
+1 781 482 9649
Clotilde Houzé
chouze0@shire.com +1 781 266 3567
SHIRE and the Shire Logo are
registered trademarks of Shire Pharmaceutical Holdings Ireland
Limited or its affiliates.
Mydayis is a trademark of Shire
LLC.
Forward-Looking Statements
Statements included herein that are not historical facts,
including without limitation statements concerning future strategy,
plans, objectives, expectations and intentions, the anticipated
timing of clinical trials and approvals for, and the commercial
potential of, inline or pipeline products, 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 adversely affected. The risks and uncertainties
include, but are not limited to, the following:
• Shire’s products may not be a commercial success;
• increased pricing pressures and limits on patient access as a
result of governmental regulations and market developments may
affect Shire’s future revenues, financial condition and results of
operations;
• Shire conducts its own manufacturing operations for certain of
its products and is reliant on third party contract manufacturers
to manufacture other products and to provide goods and services.
Some of Shire’s products or ingredients are only available from a
single approved source for manufacture. Any disruption to the
supply chain for any of Shire’s 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 for
some period of time;
• the manufacture of Shire’s products is subject to extensive
oversight by various regulatory agencies. Regulatory approvals or
interventions associated with changes to manufacturing sites,
ingredients or manufacturing processes could lead to, among other
things, significant delays, an increase in operating costs, lost
product sales, an interruption of research activities or the delay
of new product launches;
• certain of Shire’s therapies involve lengthy and complex
processes, which may prevent Shire from timely responding to market
forces and effectively managing its production capacity;
• Shire has a portfolio of products in various stages of
research and development. The successful development of these
products is highly uncertain and requires significant expenditures
and time, and there is no guarantee that these products will
receive regulatory approval;
• the actions of certain customers could affect Shire’s ability
to sell or market products profitably. Fluctuations in buying or
distribution patterns by such customers can adversely affect
Shire’s revenues, financial conditions or results of
operations;
• Shire’s products and product candidates face substantial
competition in the product markets in which it operates, including
competition from generics;
• adverse outcomes in legal matters, tax audits and other
disputes, including Shire’s ability to enforce and defend patents
and other intellectual property rights required for its business,
could have a material adverse effect on the Company’s revenues,
financial condition or results of operations;
• inability to successfully compete for highly qualified
personnel from other companies and organizations;
• failure to achieve the strategic objectives, including
expected operating efficiencies, cost savings, revenue
enhancements, synergies or other benefits at the time anticipated
or at all with respect to Shire’s acquisitions, including NPS
Pharmaceuticals Inc., Dyax Corp. or Baxalta Incorporated may
adversely affect Shire’s financial condition and results of
operations;
• Shire’s growth strategy depends in part upon its ability to
expand its product portfolio through external collaborations,
which, if unsuccessful, may adversely affect the development and
sale of its products;
• a slowdown of global economic growth, or economic instability
of countries in which Shire does business, as well as changes in
foreign currency exchange rates and interest rates, that adversely
impact the availability and cost of credit and customer purchasing
and payment patterns, including the collectability of customer
accounts receivable;
• failure of a marketed product to work effectively or if such a
product is the cause of adverse side effects could result in damage
to Shire’s reputation, the withdrawal of the product and legal
action against Shire;
• 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
significant legal costs and the payment of substantial compensation
or fines;
• Shire is dependent on information technology and its systems
and infrastructure face certain risks, including from service
disruptions, the loss of sensitive or confidential information,
cyber-attacks and other security breaches or data leakages that
could have a material adverse effect on Shire’s revenues, financial
condition or results of operations;
• Shire incurred substantial additional indebtedness to finance
the Baxalta acquisition, which may decrease its business
flexibility and increase borrowing costs; and
a further list and description of risks, uncertainties and other
matters can be found in Shire’s most recent Annual Report on Form
10-K and in Shire’s subsequent Quarterly Reports on Form 10-Q, in
each case including those risks outlined in “ITEM 1A: Risk
Factors”, and in Shire’s subsequent reports on Form 8-K and other
Securities and Exchange Commission filings, all of which are
available on Shire’s website.
All forward-looking statements attributable to us or any person
acting on our behalf are expressly qualified in their entirety by
this cautionary statement. Readers are cautioned not to place undue
reliance on these forward-looking statements that speak only as of
the date hereof. Except to the extent otherwise required by
applicable law, we do not undertake any obligation to update or
revise forward-looking statements, whether as a result of new
information, future events or otherwise.