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FDA Approves New Celebrex (Celecoxib) Prescribing Information; New Data Included From CLASS Study

PEAPACK, NJ -- June 7, 2002 -- Pharmacia Corporation and Pfizer Inc today announce that after a comprehensive review of the Celecoxib Long-term Arthritis Safety Study (CLASS) data, the U. S. Food and Drug Administration (FDA) has approved revised labeling for Celebrex® (celecoxib capsules). This prospective, long-term safety outcomes study was designed to evaluate gastrointestinal (GI) safety of Celebrex at supra therapeutic doses for osteoarthritis (OA) and rheumatoid arthritis (RA) compared to common therapeutic doses of diclofenac and ibuprofen. The study also provided new information about cardiovascular (CV) safety, hypertension, edema and hematologic events.

New label reaffirms the GI and CV safety profile of Celebrex

Specifically, the new prescribing information includes additional GI safety data from CLASS. Importantly, the revised label also includes data indicating that there was no increased risk for serious CV adverse events observed compared to the non-specific NSAID comparators (diclofenac and ibuprofen). These CV events included heart attack, stroke and unstable angina.

The revised label includes data through nine months of treatment. This timepoint was the median duration of exposure for Celebrex and diclofenac groups and there were no new safety signals beyond this timepoint.

Upper GI Safety Profile
Upper GI ulcers, gross bleeding or perforation are adverse events similar to, but not identical to, complicated and symptomatic ulcers. The primary endpoint of CLASS was the incidence of complicated ulcers -- gastrointestinal bleeding, perforation or obstruction. Differences in the incidence of complicated ulcers between Celebrex and the combined group of non-specific NSAID comparators were not statistically significant. One possible explanation may be due to confounding factors such as premature discontinuation of non-specific NSAID patients and concurrent aspirin use, a risk factor for GI events.

Labeling for prescription NSAIDs show an annual rate of upper GI ulcer, gross bleeding or perforations of about 2-4% in patients treated for one year. The new label reflects nine-month data from CLASS showing that the estimated cumulative incidence of upper gastrointestinal (GI) complicated and symptomatic ulcers for Celebrex is 0.78% even at doses higher than FDA approved doses of Celebrex for osteoarthritis (OA) and rheumatoid arthritis (RA) respectively.

Estimated cumulative incidence of upper GI complicated ulcers was 0.32% in the Celebrex non-aspirin users. In addition to the CLASS study, the GI safety profile of Celebrex is supported by a large clinical database of more than 30,000 patients that includes the New Drug Application (NDA) and the largest OA study conducted to date, SUCCESS-1.

"Physicians recognize that the COX-2 specific inhibitors, such as celecoxib, represent an advance in the treatment of osteoarthritis and adult rheumatoid arthritis because of their upper GI safety profiles," said Andrew Whelton, M.D., a nephrologist/clinical pharmacologist, Adjunct Professor of Medicine, Johns Hopkins University School of Medicine. "Beyond the demonstrated GI safety profile of the coxibs, physicians should also consider safety across all organ systems when weighing the net risks for patients with chronic conditions such as OA and RA," Dr. Whelton said.

It is estimated that there are more than 16,000 NSAID-related deaths every year among OA and RA patients in the United States, and the annual number of hospitalizations in the United States for serious GI complications is 107,000. At a conservative estimated cost of $10,000 to $15,000 per hospitalization, the annual costs exceed $1 billion.

Cardiovascular Safety Profile
The revised label reaffirms the cardiovascular safety profile of Celebrex. Analysis of the safety data from CLASS shows there were no significant differences between treatment groups in the overall incidence of serious CV thromboembolic adverse events, such as heart attack, stroke and unstable angina. This is observed at doses of 400 mg twice a day -- a dose range which is higher than FDA approved doses of Celebrex for OA, RA and acute pain. The cumulative rates of such events in all patients at nine months for Celebrex, diclofenac and ibuprofen were 1.2%, 1.4% and 1.1%, respectively. The rates for heart attacks in each of the three non-aspirin treatment groups were less than 0.2%.

The incidences of hypertension and edema were similar across the three treatment groups. The rates of hypertension for Celebrex, diclofenac and ibuprofen were 2.4%, 4.2% and 2.5%, respectively.

Additionally, the Celebrex cardiovascular safety profile is supported by the studies conducted for the New Drug Application (NDA) and other post- marketing surveillance worldwide covering an estimated 34.5 million patients or 17.25 million patient-years of exposure (assuming an average treatment period of six months) and is consistent with data reported to the FDA.

Hematological Data
Hemoglobin was measured in this GI safety study to detect anemia. In CLASS, patients taking Celebrex 400 mg twice a day experienced a lower incidence of clinically significant decreases in hemoglobin (>2g/dL) compared to patients taking either diclofenac 75 mg twice a day or ibuprofen 800 mg three times a day: 0.5%, 1.3% and 1.9% respectively. The lower incidence of events with Celebrex(R) was maintained with or without aspirin use. In addition, Celebrex does not inhibit platelet aggregation or effect bleeding time at indicated dosages.

Additional Information
CLASS was a prospective, long-term, safety outcome study conducted postmarketing in approximately 8,000 osteoarthritis (OA) and rheumatoid arthritis (RA) patients who were enrolled regardless of disease severity and prophylactic aspirin use. Use of low-dose aspirin was found to be a significant risk factor in this study. Patients taking Celebrex and aspirin experienced three-fold higher rates of complicated ulcers compared to those taking aspirin alone.

Celebrex is the COX-2 specific inhibitor with the broadest range of approved indications in the U.S., including the treatment of osteoarthritis (OA), adult rheumatoid arthritis (RA) and the management of acute pain and primary dysmenorrhea in adults. In addition, Celebrex is approved to reduce the number of adenomatous colorectal polyps in familial adenomatous polyposis (FAP) -- a rare and devastating genetic disease that may result in colorectal cancer -- as an adjunct to usual care. Studies to date have not included a cancer endpoint, and thus Celebrex has not been proven to reduce the risk of GI cancer or the need for any FAP-related surgeries. The recommended dose for OA is 200 mg daily and for RA, 100 mg to 200 mg twice per day. The recommended dose for acute pain is 400 mg initially, followed by an additional 200 mg dose if needed on the first day. On subsequent days, the recommended dose is 200 mg twice daily as needed.

Celebrex should not be taken by patients who have aspirin-sensitive asthma or allergic reactions to aspirin or other arthritis medicines or certain sulfa drugs called sulfonamides, or who are in their third trimester of pregnancy. As with all NSAIDs, serious GI tract ulcerations can occur without warning symptoms. Physicians and patients should remain alert to the signs and symptoms of GI bleeding. Celebrex does not affect platelet function and therefore should not be used for cardiovascular prophylaxis. As with all NSAIDs, Celebrex should be used with caution in patients with fluid retention, hypertension, or heart failure. In overall clinical studies the most common side effects of Celebrex(R) were dyspepsia, diarrhea and abdominal pain, which were generally mild to moderate.

There have been infrequent post-marketing reports of increases in prothrombin time, sometimes associated with bleeding events, predominantly in the elderly. Anticoagulant activity should be monitored when therapy with Celebrex is initiated or changed in patients taking warfarin, particularly in the first few days.

The drug is co-marketed by Pharmacia Corporation and Pfizer Inc. Pharmacia Corporation (NYSE: PHA) is a top-tier global pharmaceutical company with a leading agricultural subsidiary. Pharmacia's innovative medicines and other products save lives and enhance health and wellness. Pharmacia's 59,000 people work together with many diverse stakeholders to bring these benefits to people around the world, and to create new health solutions for the future.

Pfizer Inc discovers, develops, manufactures and markets leading prescription medicines, for humans and animals, and many of the world's best-known consumer products.

Forward-Looking Information
This press release contains forward-looking or anticipatory statements about the Company's business and product performance, which are based on the information currently available. However, because these forward-looking statements are subject to new information, future developments and uncertainties over time, actual results and product performance may differ materially from those expressed or implied by these forward-looking statements. The Company undertakes no obligation to update any forward-looking statements as a result of new information or future developments.

Celebrex® is a registered trademark of Pharmacia Corporation.

For complete prescribing information on Celebrex, access http://www.celebrex.com or call toll-free 1-800-323-4204.


SOURCE: Pharmacia Corporation

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