Shire plc Regulatory Approval

 
TIDMSHP 
 
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            [e-mail] 
[phone] 
 
Robert Coates   [e-mail] 
[phone] 
Media 
 
Gwen Fisher      [e-mail] 
[phone] 
Clotilde Houzé   [e-mail]      [phone] 
 
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. 
 
 
 
END 
 

(END) Dow Jones Newswires

June 21, 2017 02:00 ET (06:00 GMT)