A phase II trial of lisdexamfetamine dimesylate (NRP104), also presented at APA today, demonstrated a statistically significant reduction in ADHD symptoms comparable to mixed amphetamine salts extended-release (MAS XR). Both products were studied versus placebo in children aged 6 to 12 years with ADHD.
¡§These studies showed that NRP104 significantly reduced ADHD symptoms and was well-tolerated,¡¨ said Joseph Biederman, M.D., professor of psychiatry at Harvard Medical School and director of Pediatric Psychopharmacology at Massachusetts General Hospital. Dr. Biederman led both of the NRP104 studies presented at the APA meeting.
New River Pharmaceuticals Inc. developed NRP104 and on January 31, 2005, signed a collaborative agreement with Shire to develop and commercialize the product. On December 6, 2005 New River filed a New Drug Application with U.S. Food and Drug Administration to evaluate NRP104 for the treatment of ADHD. This application is currently under review.
Phase III Study Results of NRP104
In the phase III study, 30-milligram (mg), 50 mg, and 70 mg QD doses of lisdexamfetamine dimesylate (NRP104) demonstrated significant improvements in average ADHD symptoms compared with placebo (P<0.0001) after four weeks of once-daily treatment, as measured by 230 children¡¦s scores on the ADHD Rating Scale (ADHD-RS). ADHD-RS is a standard test for diagnosing ADHD in children and adolescents and for assessing their response to treatment. The scale, which contains 18 items, is based on the ADHD diagnosis criteria as defined in the APA¡¦s Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision„µ.
Average reductions in ADHD-RS scores were 51 percent (21.8 points), 54 percent (23.4 points) and 59 percent (26.7 points) for the 30 mg, 50 mg, and 70 mg dosage strengths, respectively, compared to baseline. All three NRP104 doses produced significant average differences in the scores during the first week of treatment (P<0.0001 versus placebo for each dose). Of the participants, 36 percent had previously received treatment for ADHD.
Each of the three dosage strengths (30 mg, 50 mg and 70 mg per day) demonstrated efficacy in the morning (~10:00 am); afternoon (~2:00 pm); and into evening (~6:00 pm), compared to placebo, as demonstrated by the Conners¡¦ ADHD Rating Scale ¡V Parent (CPRS).
Most adverse events were mild to moderate and occurred in the first week. The most common adverse events were decreased appetite, insomnia, headache and upper abdominal pain.
Phase II Study Results of NRP104
In a phase II three-way double-blind cross-over analog classroom study, investigators optimized 50 children aged 6 to 12 years to their MAS XR dose during a three-week period. The researchers then randomized the participants to receive one week each of lisdexamfetamine dimesylate (NRP104) (approximate equivalent dose to the child¡¦s optimal MAS XR dose), MAS XR (subject¡¦s optimal dose) or a placebo for a total of three weeks.
The results demonstrated consistently improved behavior when receiving either NRP104 or MAS XR as measured by the Swanson, Kotkin, Agler, M-Flynn and Pelham (SKAMP) deportment rating scale, which is a standard, validated classroom assessment tool used for testing ADHD treatment. Both NRP104 and MAS XR treatments resulted in significant and equivalent improved deportment (0.8 for both), versus placebo (1.7) (P<0.0001, for both).
The results also demonstrated that children¡¦s academic productivity significantly improved with both NRP104 and MAS XR treatments, compared to placebo, as measured by PERMP, an age-adjusted collection of math problems that provides an accurate measure of a child¡¦s ability to pay attention and stay on task correlated by an increase in number of successfully completed problems. Average scores on PERMP-attempted were NRP104, 133.3, and MAS XR, 133.6, compared to placebo, 88.2, (P<0.0001, for both) and on PERMP-correct, NRP104, 129.6, and MAS XR, 129.4, compared to placebo, 84.1 (P<0.0001).
Adverse events were mild to moderate. The most common adverse events for NRP104 were insomnia (8 percent), decreased appetite (6 percent) and anorexia (4 percent); for MAS XR were decreased appetite (4 percent), upper abdominal pain (4 percent), insomnia (2 percent), and vomiting (2 percent).
For further information, please contact:
Marion Glick ¡V Porter Novelli, 212-601-8273; on-site 917-301-4206
Janice Miller ¡V Porter Novelli , 212-601-8176; on-site 917-494-6315
New River Pharmaceuticals conducted and sponsored both clinical trials of NRP104.
About NRP104
NRP104 was designed as a pharmacologically inactive prodrug in which d-amphetamine is covalently bonded to l-lysine, a naturally occurring amino acid. It is not until undergoing hydrolysis that the pharmacologically active d-amphetamine molecule is gradually released, which may make drug tampering difficult and impractical. NRP104 was designed with the expectation to have comparable efficacy and tolerability to currently marketed once daily extended-release stimulants with reduced potential for abuse, diversion and overdose toxicity.
¡§We believe the design of NRP104 could yield a reduced potential for abuse and diversion, while also providing effectiveness comparable to currently marketed ADHD medications. We are continuing to study NRP104 to further evaluate the compound¡¦s potential,¡¨ says Suma Krishnan, New River¡¦s Vice-President, Product Development.
About ADHD
ADHD affects approximately 7.8 percent of all school-age children, or about 4.4 million U.S. children aged 4 to 17 years, according to the U.S. Centers for Disease Control and Prevention. ADHD is considered the most commonly diagnosed psychiatric disorder in children. 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.
Shire plc
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), SPD476 (ulcerative colitis), idursulfase (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 Securities and Exchange Commission, including Shire plc¡¦s Annual Report on Form 10-K for the year ended December 31, 2005.
New River Pharmaceuticals Inc.
New River Pharmaceuticals Inc. is a specialty pharmaceutical company developing novel pharmaceuticals that are generational improvements of widely prescribed drugs in large and growing markets.
For further information on New River, please visit the Company¡¦s website: www.nrpharma.com
"SAFE HARBOR" STATEMENT UNDER THE PRIVATE SECURITIES LITIGATION REFORM ACT OF 1995
This press release contains certain forward-looking information that is intended to be covered by the safe harbor for "forward-looking statements" provided by the Private Securities Litigation Reform Act of 1995. Forward- looking statements are statements that are not historical facts. Words such as "expect(s)," "feel(s)," "believe(s)," "will," "may," "anticipate(s)" and similar expressions are intended to identify forward-looking statements. These statements include, but are not limited to, financial projections and estimates and their underlying assumptions; statements regarding plans, objectives and expectations with respect to future operations, products and services; and statements regarding future performance. Such statements are subject to certain risks and uncertainties, many of which are difficult to predict and generally beyond the control of New River Pharmaceuticals, that could cause actual results to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include: those discussed and identified in the New River Pharmaceuticals Inc. annual report on Form 10-K, filed with the SEC on March 15, 2006; the timing, progress and likelihood of success of our product research and development programs; the timing and status of our preclinical and clinical development of potential drugs; the likelihood of success of our drug products in clinical trials and the regulatory approval process; our drug products' efficacy, abuse and tamper resistance, onset and duration of drug action, ability to provide protection from overdose, ability to improve patients' symptoms, incidence of adverse events, ability to reduce opioid tolerance, ability to reduce therapeutic variability, and ability to reduce the risks associated with certain therapies; the ability to develop, manufacture, launch and market our drug products; our projections for future revenues, profitability and ability to achieve certain sales targets; our estimates regarding our capital requirements and our needs for additional financing; the likelihood of obtaining favorable scheduling and labeling of our drug products; the likelihood of regulatory approval under the Federal Food, Drug, and Cosmetic Act without having to conduct long and costly trials to generate all of the data which are often required in connection with a traditional new chemical entity; our ability to develop safer and improved versions of widely prescribed drugs using our Carrierwave (TM) technology; and our ability to obtain favorable patent claims. Readers are cautioned not to place undue reliance on these forward- looking statements that speak only as of the date hereof. New River Pharmaceuticals does not undertake any obligation to republish revised forward-looking statements to reflect events or circumstances after the date hereof or to reflect the occurrence of unanticipated events. Readers are also urged to carefully review and consider the various disclosures in New River Pharmaceuticals' annual report on Form 10-K, filed with the SEC on March 15, 2006, as well as other public filings with the SEC.
Wednesday, May 24, 2006 at 12:00 PM EST, NR632
Efficacy and Safety of NRP104 in Children Aged 6 to 12 Years With Attention-Deficit/Hyperactivity Disorder (ADHD)
Joseph Biederman, et.al.
Wednesday, May 24, 2006 at 12:00 PM EST, NR631
Improvements in Symptoms of Attention-Deficit/Hyperactivity Disorder in School-aged Children With NRP104 and Extended-Release Mixed Amphetamine Salts Versus Placebo
Joseph Biederman, et.al.