a significant seizure reduction in line with that seen in the three previously published pivotal epilepsy studies.

• Celebrex and Bextra

On April 7, 2005, the FDA announced a decision to require boxed warnings of potential cardiovascular risk for all COX-2 pain relievers and all prescription NSAIDs, including older non- specific drugs such as ibuprofen and naproxen. On July 29, 2005, Pfizer and the FDA finalized the label changes for Celebrex. The final U.S. label contains a boxed warning of potential serious cardiovascular and gastrointestinal risks for Celebrex that are consistent with warnings for all other prescription NSAIDs. The boxed warning provides that Celebrex is contraindicated for patients who recently have undergone coronary artery bypass graft surgery. The label recommends that Celebrex be prescribed at the lowest effective dose for the shortest duration consistent with individual patient treatment goals. Pfizer is continuing to conduct additional clinical studies evaluating the benefits and risks of Celebrex. Pfizer is supporting Cleveland Clinic’s 20,000 patient prospective study to definitively evaluate the relative safety of Celebrex and two older pain medications in patients with heart disease or at high risk of heart disease.

In June 2005, the Committee for Human Medicinal Products (CHMP) concluded its COX-2 referral process and recommended that both Celebrex and Dynastat (parecoxib) remain available to patients. The European Medicines Evaluation Agency (EMEA) has required new labeling for all COX-2 drugs that includes a restriction on use for patients with established heart disease or stroke and additional warnings to physicians regarding use in patients with cardiovascular risk factors. This new labeling was implemented for all COX-2 medicines across the E.U. in July of 2005. The market for pain relievers has changed since the withdrawal of Vioxx in September 2004. Sales of Celebrex began to decline in late 2004 due to physician and patient concerns surrounding selective COX-2 inhibitors. Also contributing to the decline in sales of Celebrex was the voluntary suspension of DTC advertising in the U.S. beginning in December 2004. Pfizer plans to reintroduce branded advertising in 2006, in alignment with our new DTC advertising principles, highlighting Celebrex’s unique clinical profile and benefits.

In September 2005, with full implementation of revised labeling, Pfizer began to focus renewed attention on Celebrex, with the goal of making the pain reliever available to increased numbers of patients. In July 2005, the FDA approved a sixth indication for Celebrex—ankylosing spondylitis—a form of spinal arthritis that affects more than one million people in the U.S.

In April 2005, the FDA decided that while Bextra’s cardiovascular risk could not be differentiated from other NSAIDs, the additional, increased risk of rare but serious skin reactions associated with Bextra, already described in its label, warranted its withdrawal from the market. In 2004, we recorded $1.3 billion in revenue for Bextra. We respectfully disagree with the FDA’s position regarding the relative risk/benefit profile of Bextra. However, in