Analysis of Ulcerative Colitis (UC) Time to Symptom Resolution Data from Pivotal...

Analysis of Ulcerative Colitis (UC) Time to Symptom Resolution Data from
Pivotal Study of LIALDA(TM) (mesalamine) Presented at DDW

SAN DIEGO, May 20 /PRNewswire-FirstCall/ -- A post hoc analysis showing
time to symptom resolution data from a study (study 302) of Shire plc's
(LSE: SHP, Nasdaq: SHPGY) ulcerative colitis (UC) drug, LIALDA(TM), will be
presented today at Digestive Disease Week (DDW). Study 302 (further referred
to as "Kamm study," led by Dr Michael A. Kamm, from St Mark's Hospital in
London, UK), demonstrated LIALDA was effective in inducing remission in
patients with active, mild to moderate ulcerative colitis compared to placebo
and these study results were published in the January 2007 issue of
Gastroenterology.
"The time between initiation of therapy and initial symptom resolution is
an important endpoint in the treatment of UC for both patients and
physicians," said Gary Lichtenstein, director of the Inflammatory Bowel
Disease Program at the University of Pennsylvania, investigator on this post
hoc analysis. "This analysis was important as it showed LIALDA benefits
patients by significantly lowering the time it takes patients to experience
relief from their UC symptoms as compared to placebo."
Time to initial symptom resolution on LIALDA
Poster Presentation: May 20, 2008, San Diego Convention Center -- Sails
Pavilion, #T1140
A post hoc analysis of the Kamm study (study 302) examined the treatment
time required for patients to experience initial symptom resolution over eight
weeks. In this analysis, time to initial symptom resolution was assessed as
either the time between the first dose of study medication and the first day
of symptom resolution (rectal bleeding or normalization of stool frequency or
both) or the time between the first dose of study medication and the first day
of three consecutive days of symptom resolution. Initial symptom resolution of
rectal bleeding, normalization of stool frequency or both was assessed by a
modified UC-Disease Activity Index (UC-DAI) scoring system. Resolution of
symptoms was defined for both rectal bleeding and stool frequency as a
modified UC-DAI sub-score of 0.
Overall, a total of 341 patients with active, mild to moderate UC were
analyzed as part of this post hoc analysis of an 8-week study. Patients in the
Kamm study received LIALDA 2.4g/day once daily (n=84), 4.8g/day once daily
(n=85), Asacol 2.4g/day three times daily (n=86); or placebo (n=86).
The post hoc analysis found that regardless of the definition used for
remission, treatment with LIALDA 2.4g/day, or 4.8g/day, or Asacol 2.4g/day
resulted in similar median times to symptom resolution that were shorter than
placebo. The Kamm study was not designed to compare LIALDA to Asacol. Asacol
was included in the study as a reference arm only.
-- Symptom resolution of rectal bleeding at the first day and first of
three days, respectively:
-- LIALDA 2.4g/day: 9 days and 18 days
-- LIALDA 4.8g/day: 9 days and 17 days
-- Placebo: 14 days and 35 days

-- Normalization of stool frequency at the first day and first of three
days, respectively:
-- LIALDA 2.4g/day: 20 days and 33 days
-- LIALDA 4.8g/day: 23 days and 38 days
-- Placebo: 38 days and 53 days

-- Resolution of both rectal bleeding and normalization of stool
frequency at the first day and first of three days, respectively:
-- LIALDA 2.4g/day: 27 days and 37 days
-- LIALDA 4.8g/day: 29 days and 45 days
-- Placebo: 44 days and 56 days

Important Safety Information for LIALDA
LIALDA tablets are indicated for the induction of remission in patients
with active, mild to moderate ulcerative colitis. Safety and effectiveness of
LIALDA beyond 8 weeks have not been established.
LIALDA is contraindicated in patients with hypersensitivity to salicylates
(including mesalamine) or to any of the components of LIALDA. Caution should
be exercised when treating patients with pyloric stenosis or those allergic to
sulfasalazine. Mesalamine has been associated with an acute intolerance
syndrome (3 percent of patients in clinical trials with mesalamine or
sulfasalazine) that may be difficult to distinguish from a flare of
inflammatory bowel disease. If acute intolerance syndrome is suspected, prompt
withdrawal is required.
Mesalamine-induced cardiac hypersensitivity reactions (myocarditis and
pericarditis) have been reported. Reports of renal impairment have been
associated with mesalamine medications. In patients with renal impairment,
caution should be exercised, and LIALDA should be used only if the benefits
outweigh the risks. No information is available for patients with hepatic
impairment.
LIALDA is generally well tolerated. The majority of adverse events in the
double-blind, placebo-controlled trials were mild or moderate in severity. In
clinical trials (n=535), the most common treatment-related adverse events with
LIALDA 2.4g/day, 4.8g/day and placebo were headache (5.6 percent, 3.4 percent
and 0.6 percent, respectively) and flatulence (4 percent, 2.8 percent and 2.8
percent, respectively). Pancreatitis occurred in less than 1 percent of
patients during clinical trials and resulted in discontinuation of therapy
with LIALDA.
For more information about LIALDA and for Full Prescribing Information,
please visit http://www.LIALDA.com.
About LIALDA
LIALDA is part of a drug class called aminosalicylates, which contain 5-
aminosalicyclic acid (5-ASA). 5-ASA is a well-established drug of choice and
often a first-line treatment for UC. LIALDA is indicated for the induction of
remission in patients with active, mild to moderate UC. The safety and
efficacy of LIALDA have been established for up to eight weeks. LIALDA is the
first new formulation in this class to be approved since 2000. LIALDA is the
only ulcerative colitis treatment that utilizes MMX(R) Technology. LIALDA
with MMX Technology combines a pH dependent gastro-resistant coating, which
delays the release of the medication to the colon (the site of the
inflammation in ulcerative colitis), with a tablet core containing mesalamine
with hydrophilic and lipophilic components.
Shire has licensed from Giuliani SpA the exclusive rights to develop and
commercialize LIALDA in the US, Canada, Pacific Rim, and Europe (excluding
Italy). LIALDA is known as MEZAVANT XL(TM) in the UK and Ireland, and
MEZAVANT(R) elsewhere outside of the US. Giuliani SpA retains the development
and commercialization rights in Italy. Cosmo Pharmaceuticals SpA, Milan,
developed the MMX technology.
SHIRE PLC
Shire's strategic goal is to become the leading specialty
biopharmaceutical company that focuses on meeting the needs of the specialist
physician. Shire focuses its business on attention deficit and hyperactivity
disorder (ADHD), human genetic therapies (HGT), gastrointestinal (GI) and
renal diseases. The structure is sufficiently flexible to allow Shire to
target new therapeutic areas to the extent opportunities arise through
acquisitions. 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. Shire believes that a carefully
selected portfolio of products with strategically aligned 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.
For further information please contact:

Media Sarah McGee (GolinHarris) +1 312 729 4125
Matthew Cabrey (Shire) +1 484 595 8248

About DDW
DDW is the largest international gathering of physicians, researchers and
academics in the fields of gastroenterology, hepatology, endoscopy and
gastrointestinal surgery. Jointly sponsored by the American Association for
the Study of Liver Diseases, the American Gastroenterological Association
(AGA) Institute, the American Society for Gastrointestinal Endoscopy and the
Society for Surgery of the Alimentary Tract, DDW takes place May 17-22, 2008,
at the San Diego Convention Center, San Diego, CA. The meeting showcases
approximately 5,000 abstracts and hundreds of lectures on the latest advances
in GI research, medicine and technology. For more information, visit
http://www.ddw.org.
THE "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'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 including, but not limited to the successful development of
JUVISTA(R) (Human TGFB3) and veleglucerase alfa (GA-GCB); manufacturing and
commercialization including, but not limited to, the establishment in the
market of VYVANSE(TM) (lisdexamfetamine dimesylate) (Attention Deficit and
Hyperactivity Disorder ("ADHD")); the impact of competitive products,
including, but not limited to, the impact of those on Shire's ADHD franchise;
patents, including but not limited to, legal challenges relating to Shire's
ADHD franchise; government regulation and approval, including but not limited
to the expected product approval date of INTUNIV(TM) (guanfacine extended
release) (ADHD); Shire'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 filings with the Securities and Exchange Commission,
particularly Shire plc's Annual Report on Form 10-K for the year ended
December 31, 2007.
LIALDA(TM) is a trademark of Shire LLC.
MMX(R) is a trademark owned by Cosmo Technologies Ltd, Ireland, a
wholly-owned subsidiary of Cosmo Pharmaceuticals SpA.
SOURCE Shire plc

Sarah McGee of GolinHarris, +1-312-729-4125, for Shire; or Matthew Cabrey of
Shire, +1-484-595-8248