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"Shire is proud to introduce INTUNIV, providing clinicians, patients, andtheir families with a novel ADHD treatment option," said Mike Cola, Presidentof Shire Specialty Pharmaceuticals. "This is a complex disorder in whichpatients may present with multiple symptoms and behaviors that can bedisruptive. INTUNIV expands the Shire ADHD portfolio with a nonscheduledmedication, allowing clinicians to optimize their overall approach towardmanaging ADHD and may help provide symptom control for children and teenswith ADHD who often have difficulty responding appropriately to everydaysituations and challenges."
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Once-daily INTUNIV is expected to be available in US pharmacies inNovember and will come in four dosage strengths (1 mg, 2 mg, 3 mg, and 4 mg).INTUNIV will be marketed in the United States by the existing Shire ADHDsales team of nearly 600 representatives. INTUNIV is not a controlledsubstance and has no known potential for abuse or dependence.
"Everyday situations and challenges may be difficult for children andadolescents with ADHD as it is a disruptive disorder that includes symptomsand behaviors such as being easily distracted, always on the go, interruptingothers, arguing with adults, or temper outbursts," said Frank A. Lopez, MD, aneurodevelopmental pediatrician in private practice at Children'sDevelopmental Center in Winter Park, Florida. "In clinical trials, INTUNIV, aselective alpha-2A receptor agonist, significantly reduced ADHD symptomsacross a full day as measured by parents at 6 pm, 8 pm, and 6 am the nextmorning. This is important because children with ADHD require symptom controlat home, school, and during after school activities."
The introduction of INTUNIV is consistent with the strategy of Shire toexpand and diversify its ADHD portfolio, which now consists of four ADHDtreatment options of scheduled and nonscheduled medicines in the UnitedStates and two ADHD medicines available outside the United States.
Additional information about INTUNIV and Full Prescribing Information areavailable at http://www.intuniv.com.
INTUNIV Demonstrated Significant Reduction in ADHD Symptoms
The efficacy of INTUNIV in the treatment of ADHD was established in two,similarly designed, placebo-controlled clinical trials in children andadolescents aged 6 to 17 years who met Diagnostic and Statistical Manual ofMental Disorders-IV (DSM-IV(R)) criteria for ADHD. Statistically significantimprovements were reported by investigators, parents, and teachers.
The first pivotal trial was a phase III, double-blind, parallel-grouptrial, in which investigators randomized 345 children aged 6 to 17 years toeither a placebo or a fixed 2-mg, 3-mg, or 4-mg dose of INTUNIV given oncedaily during an eight-week period. The second pivotal trial was a phase III,double-blind, parallel-group trial, in which investigators randomized 324children aged 6 to 17 years to either a placebo or a fixed 1-mg, 2-mg, 3-mg,or 4-mg dose of INTUNIV given once daily during a nine-week period, with the1 mg assigned only to patients weighing less than 50 kg (110 lbs).
In both trials, doses were increased in increments of 1 mg per week, andinvestigators evaluated participants' signs and symptoms of ADHD on aonce-weekly basis using the clinician administered and scored ADHD RatingScale-IV (ADHD-RS-IV), a scale frequently used in ADHD clinical trials thatassesses hyperactive, impulsive, and inattentive symptoms. The primaryoutcome was the change in total ADHD-RS-IV scores from baseline to end pointin both studies.
Both trials demonstrated statistically significant improvements inADHD-RS-IV scores in patients taking INTUNIV beginning one to two weeks afterpatients began receiving once-daily doses of INTUNIV. In the first pivotaltrial, the mean reduction in ADHD-RS-IV total scores at end point were -16.7for INTUNIV compared to -8.9 for placebo (P<.0001), the mean reduction inADHD-RS-IV total scores in the second pivotal trial were -19.6 for INTUNIVand -12.2 for placebo (P=.0040). Placebo-adjusted LS mean changes frombaseline were statistically significant for all INTUNIV doses in therandomized treatment groups in both studies.
Additional secondary efficacy outcome measures included the Conners'Parent Rating Scale-Revised: Short Form (CPRS-R) and the Conners' TeacherRating Scale-Revised: Short Form (CTRS-R). CPRS-R and CTRS-R arecomprehensive scales that use parent and teacher observer and self-reportratings to help assess ADHD and evaluate behavioral issues in children andadolescents. Among some of the symptoms measured were: inattentiveness/beingeasily distracted, running around or climbing excessively, arguing withadults, losing temper, and interrupting or intruding on others. Significantimprovements were seen on both scales: based on the CPRS-R, parents reportedsignificant improvement across a full day (as measured at 6 pm, 8 pm, and 6am the next morning); based on the CTRS-R, which was used only in the firstpivotal trial, teachers reported significant improvement throughout theschool day (as measured at 10 am and 2 pm).
Investigators also measured the efficacy of INTUNIV with the ClinicalGlobal Impressions-Improvement (CGI-I) scale, a standard assessment used torate the improvement of a patient's illness over the course of the study. Thefirst pivotal trial found the percentage of subjects taking INTUNIV who wererated "much improved" or "very much improved" at end point ranged fromapproximately 50 to 56 percent across all doses versus approximately 26percent for placebo (P<.05). Subjects taking INTUNIV in the second pivotaltrial who rated "much improved" or "very much improved" at end point rangedfrom 54 to 56 percent across 1-mg (P=.0070), 3-mg (P=.0060), and 4-mg(P=.0040) doses versus 30 percent for placebo; the placebo-INTUNIV differencefor the 2-mg dose was not significant (P=.1404).
Safety was also evaluated during these pivotal trials and safety datashowed that adverse events reported by participants using INTUNIV weregenerally mild to moderate in severity, with the most common side effectsbeing sedative in nature. Sedation-related, treatment-emergent adverse eventswere among the most common and were usually transient and mild to moderate inseverity. Treatment-related adverse events greater than 10 percent includedsomnolence (32 percent), headache (26 percent), fatigue (18 percent), upperabdominal pain (14 percent), and sedation (13 percent). Small to modestchanges in blood pressure, pulse rate, and ECG parameters were observed.
Important Safety Information
INTUNIV is indicated for the treatment of Attention Deficit HyperactivityDisorder (ADHD) in children and adolescents aged 6 to 17. Efficacy wasestablished in two controlled clinical trials (8 and 9 weeks in duration).The physician electing to use INTUNIV for extended periods shouldperiodically reevaluate its long-term usefulness for the individual patient.
INTUNIV should not be used in patients with a history of hypersensitivityto guanfacine or any of its inactive ingredients or by patients taking otherproducts containing guanfacine
Hypotension, bradycardia, and syncope were observed in clinical trials.Use INTUNIV with caution in treating patients who have experiencedhypotension, bradycardia, heart block, or syncope, or who may have acondition that predisposes them to syncope; are treated concomitantly withantihypertensives or other drugs that can reduce blood pressure or heart rateor increase the risk of syncope. Heart rate and blood pressure should bemeasured prior to initiation of therapy, following dose increases, andperiodically while on therapy. Patients should be advised to avoid becomingdehydrated or overheated.
Sedation and somnolence were commonly observed in clinical trials. Thepotential for additive sedative effects with CNS depressant drugs should beconsidered. Patients should be cautioned against operating heavy equipment ordriving until they know how they respond to INTUNIV.
Common adverse reactions in patients taking INTUNIV that may bedose-related over the range of 1 to 4 mg/day include somnolence, sedation,abdominal pain, dizziness, hypotension/decreased blood pressure, dry mouth,and constipation.
About ADHD
ADHD is one of the most common psychiatric disorders in children andadolescents. Worldwide prevalence of ADHD is estimated at 5.3 percent (withlarge variability), according to a comprehensive systematic review of thistopic published in 2007 in the American Journal of Psychiatry. In the UnitedStates, approximately 7.8 percent of all school-aged children, or about 4.4million children aged 4 to 17 years, have been diagnosed with ADHD at somepoint in their lives, according to the Centers for Disease Control andPrevention (CDC). The disorder is also estimated to affect 4.4 percent of USadults aged 18 to 44 based on results from the National Comorbidity SurveyReplication. When this percentage is extrapolated to the full US populationaged 18 and over, approximately 9.8 million adults are believed to have ADHD.
ADHD is a psychiatric behavioral disorder that manifests as a persistentpattern of inattention and/or hyperactivity-impulsivity that is more frequentand severe than is typically observed in individuals at a comparable level ofdevelopment. The specific etiology of ADHD is unknown and there is no singlediagnostic test for this syndrome. Adequate diagnosis requires the use ofmedical and special psychological, educational, and social resources,utilizing diagnostic criteria such as Diagnostic and Statistical Manual ofMental Disorders-IV (DSM-IV(R)) or International Classification of Diseases10 (ICD-10).
Although there is no cure for ADHD, there are accepted treatments thatspecifically target its symptoms. Standard treatments include educationalapproaches, psychological or behavioral modification, and medication.
Notes to editors
SHIRE PLC
Shire's strategic goal is to become the leading specialtybiopharmaceutical company that focuses on meeting the needs of the specialistphysician. Shire focuses its business on attention deficit hyperactivitydisorder (ADHD), human genetic therapies (HGT) and gastrointestinal (GI)diseases as well as opportunities in other therapeutic areas to the extentthey arise through acquisitions. Shire's in-licensing, merger and acquisitionefforts are focused on products in specialist markets with strongintellectual property protection and global rights. Shire believes that acarefully selected and balanced portfolio of products with strategicallyaligned and relatively small-scale sales forces will deliver strong results.
For further information on Shire, please visit the Company's website:http://www.shire.com.
"SAFE HARBOR" STATEMENT UNDER THE PRIVATE SECURITIES LITIGATION REFORMACT OF 1995
Statements included herein that are not historical facts areforward-looking statements. Such forward-looking statements involve a numberof risks and uncertainties and are subject to change at any time. In theevent such risks or uncertainties materialize, the Company's results could bematerially adversely affected. The risks and uncertainties include, but arenot limited to, risks associated with: the inherent uncertainty of research,development, approval, reimbursement, manufacturing and commercialization ofthe Company's Specialty Pharmaceutical and Human Genetic Therapies products,as well as the ability to secure and integrate new products forcommercialization and/or development; government regulation of the Company'sproducts; the Company's ability to manufacture its products in sufficientquantities to meet demand; the impact of competitive therapies on theCompany's products; the Company's ability to register, maintain and enforcepatents and other intellectual property rights relating to its products; theCompany's ability to obtain and maintain government and other third-partyreimbursement for its products; and other risks and uncertainties detailedfrom time to time in the Company's filings with the Securities and ExchangeCommission.For further information please contact: Investor Relations Clea Rosenfeld (Rest of the World) +44-1256-894-160 Eric Rojas (North America) +1-617-551-9715 Media Jessica Mann (Rest of the World) +44-1256-894-280 Matthew Cabrey (North America) +1-484-595-8248 Debra Gemme (Porter Novelli for Shire) +1-212-601-8342
SOURCE Shire Plc
