Healthcare Industry News: Noven Pharmaceuticals
News Release - May 24, 2006
Positive Study Results for DAYTRANA(TM) (methylphenidate transdermal system) Presented at a Major Medical MeetingPHILADELPHIA, Pennsylvania, May 24 (HSMN NewsFeed) -- Shire plc (LSE: SHP, NASDAQ: SHPGY, TSX: SHQ) announced that its methylphenidate transdermal system (MTS), DAYTRANA(TM) demonstrated statistically significant reductions in the symptoms of Attention Deficit Hyperactivity Disorder (ADHD) and was generally well tolerated in patients aged 6 to 12 years in four analyses of two clinical trials reported at a major medical meeting in Toronto.
"Children with ADHD and their caregivers must manage symptom control throughout the day in a variety of settings, such as the classroom, after-school activities, or home," explained clinical trials principal investigator Sharon Wigal, Ph.D., associate clinical professor of pediatrics at the University of California Irvine Child Development Center. "These studies document that a methylphenidate transdermal 'skin' patch formulation is an effective, once-daily ADHD treatment that can result in the improvement of multiple measures of behavior and classroom performance."
DAYTRANA was approved by the U.S. Food and Drug Administration (FDA) for once-daily use to treat Attention Deficit Hyperactivity Disorder (ADHD) in children aged 6 to 12 years on April 6, 2006. DAYTRANA is the first and only non-oral medication for ADHD. Shire expects DAYTRANA to be available in pharmacies in mid 2006.
Data from phase II and phase III clinical trials presented Wednesday in Toronto demonstrated that DAYTRANA is a generally well-tolerated and effective treatment for ADHD in children as shown through improvements in the primary and secondary endpoints analyzed for children treated with DAYTRANA compared to children treated with placebo.
DAYTRANA was developed by Noven Pharmaceuticals, Inc., and combines the active ingredient, methylphenidate, with Noven's patented DOT Matrix(tm) transdermal technology. This transdermal delivery system was designed to provide continuous medication release throughout the day. The patch is designed to stay on during the normal daily activities of a child such as swimming, exercising or bathing.
Because DAYTRANA is a patch, physicians can manage the duration of its effect and potential side effects by having the patient wear the patch for a shorter time period than the recommended nine hours on a given day. The patch is available in four dosage strengths - 10 mg, 15 mg, 20 mg and 30 mg - all designed for nine-hour wear times with 12-hour efficacy.
Phase II Analog Classroom Study
The phase II analog classroom study included 79 children with ADHD. DAYTRANA was assessed during a nine-hour wear time. The participants treated with DAYTRANA demonstrated statistically significant improvement based on the primary study measure, the standard Swanson, Kotkin, Agler, M-Flynn, and Pelham-Deportment (SKAMP-D) scale, in which higher ratings reflect greater impairment. Overall, participants using DAYTRANA significantly reduced their SKAMP-D scores to an average of 3.2 points compared to an average score of 8.0 points for those on placebo (P < .0001) from baseline.
Similarly, the DAYTRANA group significantly reduced their average total scores on two secondary measures from baseline, the SKAMP-attention subscale and SKAMP total subscale, to 6.2 and 9.4, respectively, compared to those on placebo, which had scores of 9.9 and 17.9 (P <.0001 for both). Moreover, when measured at wear times of 2, 3, 4.5, 6, 7.5 and 9 hours post application, the participants treated with DAYTRANA had statistically significantly greater changes from the study start in their average SKAMP-D and average SKAMP-A scores.
Of note, at just two hours after application, 38.0 percent of those treated with DAYTRANA achieved a 30 percent reduction in their SKAMP-D score, compared to just 15.2 percent of those treated with a placebo. Similarly, at the same time point, 40.5 percent of those treated with DAYTRANA achieved a 30 percent reduction in their SKAMP-A score, compared to just 12.7 percent of those treated with a placebo.
A second analysis of this classroom study data, also presented at the meeting, revealed that overall average total scores on the standard Conners' Parent Rating Scale-Revised: Short Form (CPRS-R) were significantly lower for those receiving DAYTRANA, 20.2 points, compared to those on placebo, 35.3 points, (P < .0001) from baseline. Participants using DAYTRANA also had significantly lower average scores compared to those on placebo (P < .0001) for all four CPRS-R subscales: ADHD Index, Oppositional, Hyperactivity, and Cognitive Problems. Parents completed the CPRS-R at 11 a.m. and 3 p.m. on the last weekend day prior to all study site visits.
Phase III Study
In a phase III study, investigators randomly placed 270 participants in one of three treatment groups: a DAYTRANA patch and a placebo capsule, a placebo patch and an oral extended-release methylphenidate capsule or a placebo patch and placebo capsule. All of the groups received both a patch and a capsule daily each morning, but neither the investigators nor the participants knew to which group a child was assigned until the study ended.
In this study, the DAYTRANA patch - worn for nine hours - reduced the children's overall symptoms of ADHD, compared to a placebo (P < .0001), as measured by the ADHD Rating Scale-IV (ADHD-RS-IV), in which higher scores reflect greater impairment. By the study's end, participants' average ADHD-RS-IV scores declined 24.2 points (-56 percent) from baseline for children treated with DAYTRANA versus a decline of 10.3 points (-24 percent) for those treated with placebo. ADHD-RS-IV assesses 18 individual symptoms of ADHD, in which each symptom is scored from a range of 0 (reflecting no symptoms) to 3 (reflecting severe symptoms). The symptoms are defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision®, a publication of the APA.
When assessed using the ADHD-RS-IV inattentiveness and hyperactivity/impulsivity subscales, the participants treated with DAYTRANA had statistically significantly greater changes from the study start compared to those on placebo (P < .0001). Also, by the end of the study, 77.6 percent of the DAYTRANA participants experienced a greater than 30 percent reduction in their total ADHD-RS-IV scores, compared to just 28.7 percent of those on placebo.
A second analysis presented at the meeting of these data revealed that total scores on the standard Conners' Teacher Rating Scale-Revised: Short Form (CTRS-R) had significantly greater average reductions from the study start for those receiving methylphenidate transdermal system, 15.3 points, compared to those on placebo, 5.1 points, (P < .0001). Participants using DAYTRANA also had significantly lower average scores compared to those on placebo for all four CTRS-R subscales: ADHD Index (P < .0001), Oppositional (P <.05), Hyperactivity (P < .001), and Cognitive Problems (P < .01). Teachers completed the CTRS-R at 11 a.m. and 3 p.m. on the last weekend day prior to all study site visits. By the study end, the DAYTRANA treatment group had statistically significantly greater changes in their average CTRS-R total scores at both time points, compared to those treated with placebo (P <.001).
In both the phase II and phase III studies, DAYTRANA was generally well tolerated during both the dose optimization and double-blind phases. Adverse events typically were mild to moderate, resolved with continued therapy and were consistent with known effects of methylphenidate. Common adverse events seen in clinical trials included: decreased appetite, insomnia, nausea, vomiting, weight loss, tics, and affect lability (mood swings).
Shire funded these studies.
DAYTRANA is a Schedule II controlled substance. DAYTRANA was generally well tolerated in clinical studies. As with other products containing methylphenidate (the active ingredient in methylphenidate transdermal system), common side effects reported in children who received DAYTRANA were decreased appetite, insomnia, nausea, vomiting, weight loss, tics, and affect lability (mood swings).
DAYTRANA should not be used by children allergic to methylphenidate or other ingredients in DAYTRANA. The patch should be applied daily to clean, dry skin, which is free of any cuts or irritation. Avoid applying external heat to the patch. Skin irritation or allergic skin rash may occur.
Methylphenidate should not be taken by children with significant anxiety, tension, or agitation; glaucoma; tics, Tourette's syndrome, or family history of Tourette's syndrome; or current/recent use of MAO inhibitors (a type of antidepressant). Abuse of methylphenidate may lead to dependence. Tell your healthcare professional if your child has had problems with alcohol or drugs or has had depression, abnormal thoughts/behaviors, visual disturbances, seizures, high blood pressure, or heart conditions including structural abnormalities.
For Full Prescribing Information on DAYTRANA system, please visit www.ADHDSupport.com or call Shire Medical Affairs at 1-800-828-2088, option 4.
ADHD affects approximately 7.8 percent of all school-age children, more than 4 million in the United States. ADHD is considered the most commonly diagnosed psychiatric disorder in children and adolescents. ADHD is a neurological brain 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 age and maturity. If untreated, ADHD can acutely affect a child's life, leading to problems with family members, friends, sports, after-school activities and academics.
Shire's strategic goal is to become the leading specialty pharmaceutical company that focuses on meeting the needs of the specialist physician. Shire focuses its business on central nervous system, gastrointestinal, general products and human genetic therapies. The structure is sufficiently flexible to allow Shire to target new therapeutic areas to the extent opportunities arise through acquisitions. Shire believes that a carefully selected portfolio of products with a strategically aligned and relatively small-scale sales force will deliver strong results.
Shire's focused strategy is to develop and market products for specialty physicians. Shire's in-licensing, merger and acquisition efforts are focused on products in niche markets with strong intellectual property protection either in the US or Europe.
For further information on Shire, please visit the Company's website: www.shire.com.
"SAFE HARBOR" STATEMENT UNDER THE PRIVATE SECURITIES LITIGATION REFORM ACT OF 1995
Statements included herein that are not historical facts are forwarding-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 plc's results could be materially affected. The risks and uncertainties include, but are not limited to: risks associated with the inherent uncertainty of pharmaceutical research, product development, manufacturing and commercialization; the impact of competitive products, including, but not limited to, the impact of those on Shire plc's Attention Deficit and Hyperactivity Disorder ("ADHD") franchise; patents, including but not limited to, legal challenges relating to Shire plc's ADHD franchise; government regulation and approval, including but not limited to the expected product approval dates of SPD503 (ADHD), SPD465 (ADHD), MESAVANCE TM (SPD476) (ulcerative colitis), ELAPRASE TM (I2S) (Hunter syndrome) and NRP104 (ADHD), including its scheduling classification by the Drug Enforcement Administration in the United States; Shire plc's ability to benefit from the acquisition of Transkaryotic Therapies Inc.; Shire plc's ability to secure new products for commercialization and/or development; and other risks and uncertainties detailed from time to time in Shire plc's and its predecessor registrant Shire Pharmaceuticals Group plc's filings with the US Securities and Exchange Commission, including Shire plc's Annual Report on Form 10-K for the year ended December 31, 2005.
Poster # NR734
Wednesday, May 24, 2006 at 12:00 PM EST
Attention and Deportment Ratings of Transdermal Methylphenidate in ADHD
Sharon Wigal, PhD, et al.
Poster # NR726
Wednesday, May 24, 2006 at 12:00 PM EST
Parent Rated Effects of Transdermal Methylphenidate in Children with ADHD
John Turnbow, MD, et al.
Poster # NR635
Wednesday, May 24, 2006 at 12:00 PM EST
Parent and Teacher Rated Effects of MTS and OROS
Methylphenidate in ADHD
Oscar G. Bukstein, MD, et al.
Poster # NR695
Wednesday, May 24, 2006 at 12:00 PM EST
Clinician Rated Effects of MTS and OROS Methylphenidate in Pediatric ADHD
Raun Melmed, MD, et al.
Daytrana(TM), Mesavance(TM) and Elaprase(TM) are trademarks of companies within the Shire group.
DOT Matrix(tm) is a trademark of Noven Pharmaceuticals, Inc.
Diagnostic and Statistical Manual of Mental Disorders is a registered trademark of the American Psychiatric Association.
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