Analysis of Lialda(Messalamine)UC Remission Rates

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Analysis Of Ulcerative Colitis (UC) Remission Rates From Long-term

Safety Study Of LIALDA™ (mesalamine) Presented At DDW

Article Date: 24 May 2007 - 12:00 PDT

A long-term phase III, open-label 12-14 month extension study (303)

presented at the British Society of Gastroenterology (BSG) meeting in

Glasgow, Scotland in March 2007 showed Shire plc's (LSE: SHP, NASDAQ:

SHPGY, TSX: SHQ) LIALDA™ (mesalamine) is well tolerated in mild to

moderate UC patients. Today, secondary endpoints of study 303 were

presented as post-hoc analyses at Digestive Disease Week (DDW).

Approved by the FDA on January 16, 2007, for the induction of

remission in patients with active, mild to moderate UC, LIALDA is the

first-and-only FDA-approved once-daily oral mesalamine for the

treatment of ulcerative colitis. Safety and effectiveness have been

established for up to eight weeks. LIALDA is being evaluated for

longer term use.

Long-term remission and relapse rates on LIALDA (abstract # T1296)

A post-hoc analysis of study 303 evaluated maintenance of remission

and relapse rates over 12 months. Remission was defined using

stringent clinical and endoscopic criteria: modified UC Disease

Activity Index (UC-DAI) score of & #8804;1, with scores of 0 for rectal

bleeding and stool frequency, a combined Physician's Global

Assessment and sigmoidoscopy score of & #8804;1, with a sigmoidoscopy score

reduction of & #8805;1 point from baseline and no mucosal friability.

Relapse was defined as withdrawing from the study due to a need for

alternative therapy for UC.

Overall, a total of 459 patients entered the maintenance phase of

study 303. Of these patients, 362 patients met the stringent

remission criteria (clinical and endoscopic as defined above) at

baseline (in parent studies 301 and 302 - LIALDA's eight-week, phase

III, placebo-controlled trials that demonstrated efficacy for the

induction of remission in active, mild to moderate UC) and received

LIALDA once daily (2.4g/day; n=171) or twice daily (2.4g/day; n=191)

for 12 months as part of study 303.

The analysis found that 67.8 percent of the 171 patients on once-

daily LIALDA remained in remission and 88.7 percent of these patients

remained relapse free at the end of 12 months.

" Earlier studies showed that LIALDA is effective at inducing

remission in patients with active, mild to moderate UC. We were

encouraged when we did this secondary analysis and found that more

than two-thirds of patients in the maintenance phase of study 303

remained in remission and nearly 90 percent of patients did not

relapse, " says Asher Kornbluth, M.D., Associate Clinical Professor of

Medicine at The Mount Sinai Medical Center.

Long-term remission rates regardless of 5-ASA treatment (abstract #

T1295)

Another post-hoc analysis of the 303 extension study investigated

those patients on a 5-ASA who achieved remission or were deemed to be

sufficiently controlled by the physician in study 301 (patients

received LIALDA) and study 302 [patients received LIALDA or Asacol®

(mesalamine)] to determine if they had remained in remission when

staying on or changing to LIALDA for 12 months.

A total of 198 patients who received LIALDA or Asacol in the parent

studies entered the maintenance phase of study 303 directly. Of these

patients, 151 were in clinical and endoscopic remission, while 47

were considered well enough by their physician to receive maintenance

treatment.

Study findings show approximately 75 percent (n=148/198) of patients

remained in remission on LIALDA after 12 months, regardless of

whether they were previously on LIALDA or Asacol: 73.4 percent

(58/79) for patients previously on LIALDA once or twice daily

(2.4g/day); 74.7 percent (62/83) for patients previously on LIALDA

once daily (4.8g/day); and 77.8 percent (28/36) for patients

previously on Asacol three times daily (2.4g/day).

Cumulative analysis across three studies with LIALDA as sole therapy

(abstract # T1297)

Another post-hoc analysis assessed long-term remission and relapse

rates (secondary endpoints) of study 303. The analysis evaluated data

from patients taking Lialda from all three studies: 301, 302, and

303. Patients in the parent studies (301 and 302) who did not achieve

remission after eight weeks on Lialda were eligible for enrollment in

the acute phase of study 303. In this acute phase, they were given a

higher dose of Lialda (4.8g/day, once daily) for an additional eight

weeks to induce remission. In total, 63.6 percent of patients

(n=220/346) treated with Lialda for up to 16 weeks achieved

remission.

Those patients, who achieved remission either in the parent studies

(n=125), or the acute phase of study 303 (n=95), were allowed to

enter the 12-month maintenance phase of study 303. Of the 220

patients who were in remission, 218 patients actually entered the

maintenance phase.

A combined analysis of both long-term remission rates and relapse

rates showed that of the patients who started on Lialda therapy, 56.6

percent achieved remission and remained relapse free for at least one

year.

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™ 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 excipients.

Shire has licensed from Giuliani SpA the exclusive rights to develop

and commercialize LIALDA in the U.S., Canada, Europe -- known as

MEZAVANT™ -- (excluding Italy) and the Pacific Rim. Giuliani SpA

retains the development and commercialization rights in Italy. Cosmo

Pharmaceuticals SpA, Milan, developed the MMX Technology.

For more information about LIALDA and for Full Prescribing

Information, please visit www.LIALDA.com.

About UC

UC is a type of inflammatory bowel disease that produces inflammation

and sores or ulcers along the inside of the large intestine, also

called the bowel or colon. The sores may interfere with the normal

digestive process, often causing cramping, bloating, diarrhea,

bleeding, fatigue, weight loss and frequent bowel movements. This

serious, chronic autoimmune disease affects approximately 700,000

Americans. For more information on UC, visit www.managinguc.com.

Important Safety Information

LIALDA tablets are indicated for the induction of remission in

patients with active, mild to moderate ulcerative colitis. Safety and

effectiveness of LIALDA beyond eight 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 (three 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 (four percent, 2.8 percent and 2.8

percent, respectively). Pancreatitis occurred in less than one

percent of patients during clinical trials and resulted in

discontinuation of therapy with LIALDA.

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

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.

Giuliani SpA

Giuliani SpA, founded in 1889, is a privately owned specialty

biopharmaceutical company strategically focused in gastroenterology

and dermatology. It is currently marketing proprietary products for

the treatment and management of ulcerative colitis, Crohn's disease,

food intolerances and dermatological disorders. Giuliani's R & D

pipeline includes new chemical entities and biotechnological products

targeted to treat inflammatory and autoimmune diseases.

Cosmo Pharmaceuticals SpA

Cosmo is a speciality pharma company that aims to become a global

leader in optimized therapies for certain gastrointestinal diseases.

The company's proprietary clinical development pipeline specifically

addresses innovative treatments for IBD, such as ulcerative colitis

and Crohn's disease, and colon infections. Cosmo's most advanced

development product is LIALDA™/ MEZAVANT™, a treatment for ulcerative

colitis that is licensed globally to Giuliani and Shire

Pharmaceuticals. Cosmo's proprietary MMX Technology is at the core of

the company's product pipeline and was developed from its expertise

in formulating and manufacturing gastrointestinal drugs for

international clients at its GMP (Good Manufacturing Practice)

facilities in Lainate, Italy. For further information on Cosmo,

please visit the Company's website: www.cosmopharmaceuticals.com.

Digestive Disease Week

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 19-24, 2007, at the Washington

Convention Center, Washington, DC. 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 /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,

manufacturing and commercialization; the impact of competitive

products, including, but not limited to the impact of those on

Shire's Attention Deficit and Hyperactivity Disorder ( " 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

dates of SPD503 (guanfacine extended release) (ADHD) and SPD465

(extended release triple-bead mixed amphetamine salts) (ADHD);

Shire's ability to secure new products for commercialization and/or

development; Shire's ability to benefit from its acquisition of New

River Pharmaceuticals, Inc.; 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, 2006.

LIALDA™ is a trademark of Shire LLC.

MMX™ is a trademark owned by Cosmo Technologies Ltd, Ireland, a

wholly-owned subsidiary of Cosmo Pharmaceuticals SpA.

Asacol® is a registered trademark of Procter & Gamble Pharmaceuticals