Shire plc (LSE: SHP, NASDAQ: SHPGY, TSX: SHQ) announced today that results of three abuse liability studies with lisdexamfetamine dimesylate (NRP104), an investigational drug for the treatment of ADHD, were presented last week at the 68th annual meeting of the College on Problems of Drug Dependence (CPDD) in Scottsdale, AZ. Principal investigator Donald Jasinski, Professor of Medicine, Chief Center for Chemical Dependence, Johns Hopkins Bayview Medical Center, presented these results.
New River Pharmaceuticals Inc. (NASDAQ: NRPH) designed lisdexamfetamine dimesylate as an inactive prodrug in which d-amphetamine is bonded to l-lysine, a naturally occurring amino acid. Lisdexamfetamine dimesylate remains inactive until converted and active d-amphetamine is gradually released. On January 31, 2005, New River signed a collaborative agreement with Shire to develop and commercialize the product and on December 6, 2005, filed a New Drug Application with the U.S. Food and Drug Administration to evaluate lisdexamfetamine dimesylate for the treatment of ADHD. This application is currently under review.
Results of "Pharmacokinetics of oral NRP104 (lisdexamfetamine dimesylate) versus d-amphetamine in healthy adults with a history of stimulant abuse"
The A01 study was designed to evaluate the safety, tolerability, and abuse liability of lisdexamfetamine dimesylate in twelve healthy adult volunteers with histories of stimulant abuse.
In this single blind, placebo- and active-controlled, single-dose escalation study, lisdexamfetamine dimesylate tended to be less euphoric than d-amphetamine sulfate 40 mg, and had a later peak effect. The systemic exposure to active d-amphetamine sulfate (AUC and Cmax) was dose proportional following a single administration of lisdexamfetamine dimesylate in doses between 30 mg and 130 mg and was attenuated between 130 mg and 150 mg. Overall, doses of lisdexamfetamine dimesylate from 30 mg to 150 mg were well tolerated in healthy adults with previous history of stimulant abuse.
Results of "Abuse liability of intravenous L-lysine-d-amphetamine (NRP104)"
The A02 study was designed to evaluate the safety, tolerability and abuse liability of intravenously administered lisdexamfetamine dimesylate in twelve healthy adult volunteers with histories of stimulant abuse. In this double-blind, three-way crossover study, 50 mg lisdexamfetamine dimesylate taken intravenously produced a lesser degree of euphoria or amphetamine-like subjective effects, when compared to a molar weight-basis equivalent amount of 20 mg d-amphetamine sulfate taken intravenously. At the end of the study, when participants in a second cohort were asked which treatment they would take again, six participants chose intravenous d-amphetamine sulfate, two chose none of the treatments, and one chose lisdexamfetamine dimesylate.
Results of "Study to Evaluate the Likeability, Safety, and Abuse Potential of NRP104 in Adults With Histories of Stimulant Abuse"
The A03 study was designed to evaluate the "likeability" of lisdexamfetamine dimesylate compared to placebo and two active controls (d-amphetamine sulfate 40 mg, a Schedule II stimulant, and diethylpropion HCl 200 mg, a Schedule IV stimulant) in thirty-six volunteers with histories of stimulant abuse. In this double-blind, randomized, placebo and active cross-over study, lisdexamfetamine dimesylate (50 mg and 100 mg) produced liking effects that were not significantly different from placebo and were less than d-amphetamine sulfate 40 mg and diethylpropion HCl 200 mg with respect to the primary end point (DRQS Liking Score). The amphetamine content in lisdexamfetamine dimesylate 100 mg is equal to that of d-amphetamine sulfate 40 mg on a molar weight basis.
In the same study, a higher dose of lisdexamfetamine dimesylate (150 mg) produced liking effects that were significantly greater than placebo. The liking effects of lisdexamfetamine dimesylate 150 mg were not statistically significantly different from either d-amphetamine sulfate 40 mg or diethylpropion HCl 200 mg, although the amphetamine content in lisdexamfetamine dimesylate 150 mg is 50 percent more than the amphetamine content of 40 mg of d-amphetamine sulfate on a molar weight basis. Also, lisdexamfetamine dimesylate 150 mg demonstrated a delay in peak liking effects by two hours when compared to both d-amphetamine sulfate 40 mg and diethylpropion HCl 200 mg.
The results of these three human abuse liability studies suggest that the abuse liability and abuse potential of lisdexamfetamine dimesylate is less than d-amphetamine sulfate.
New River Pharmaceuticals supported the trials of lisdexamfetamine dimesylate presented at CPDD.
Notes to editors
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 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 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.
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