This is the August 28, 2017 Shire press release for its Mydayis ER tablets.

 

MYDAYIS™ (mixed salts of a single-entity amphetamine product), Shire’s New Once-Daily ADHD Treatment, Now Available in the U.S.

Mydayis, which is now available in the U.S., demonstrated improvements lasting up to 16 hours post-dose, beginning at 2 or 4 hours post-dose, compared to placebo, in total score on a skill-adjusted math test that measures attention in ADHD

Lexington, Mass., USA – August 28, 2017 – Shire plc (LSE:SHP, NASDAQ: SHPG) announced today that MYDAYIS™ (mixed salts of a single-entity amphetamine product), a once-daily, extended-release treatment comprised of three types of drug-releasing beads, is now available by prescription in the United States. The U.S. Food and Drug Administration (FDA) approved Mydayis on June 20, 2017 for patients 13 years and older with Attention Deficit Hyperactivity Disorder (ADHD). Mydayis is not for use in children 12 years and younger.

“In my practice, my patients remind me every day that each individual's needs vary; this has made it increasingly important to have different approaches to help my patients manage their ADHD symptoms,” said Dr. Matthew Brams, Assistant Professor of Clinical Psychiatry at Baylor College of Medicine. “The availability of Mydayis is a new addition to the options healthcare professionals have to consider as they help patients who continually struggle with ADHD symptoms.”

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.

The U.S. FDA approval of Mydayis was 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 at up to 16 hours post-dose, beginning at 2 to 4 hours post-dose. People living with ADHD should work with a healthcare professional to determine whether a pharmacological treatment is appropriate for them, and if so, which one meets their individual needs.

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 greater than or equal to 5% and at a rate at least twice placebo) in adults were 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.

“We recognize that patients with ADHD have varied needs when it comes to managing their symptoms,” said Perry Sternberg, Head, U.S. Commercial. “Mydayis, which has shown efficacy at up to 16 hours post-dose, beginning at 2 to 4 hours post-dose, provides a new once-daily option for appropriate patients.”

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 hourspost-dose. Across all clinical studies, adverse events were generally mild to moderate in severity and similar to those observed with other amphetamine compounds.

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. 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.

With the availability of Mydayis, Shire has patient-focused resources to share information about prescription coverage and savings, including a co-pay savings offer. This savings offer will be available for eligible commercially insured patients to help save on their Mydayis prescriptions.

Mydayis (mixed salts of a single-entity amphetamine product) Important Safety Information

What is MYDAYIS™?

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).

Serious problems can occur while taking Mydayis. Tell your healthcare provider:

• 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 totemperature 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 or your child have a seizure. Your healthcare provider will stop treatment.
• if you or your child 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 or become 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 Medication Guide, including 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.

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 is 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 healthcare professionals, patients, care givers and policymakers in order to raise awareness and broaden understanding of this condition. Learn more at www.shire.com.