Pfizer presents new approach to pain management

San Francisco, CA -- Pfizer will present data on three investigational compounds that represent potential new mechanisms for targeting pain and inflammation. These data will highlight tanezumab, a molecule designed to target nerve growth factor, a key pain mediator; CP-690,550, a JAK-inhibitor that suppresses immune-related inflammatory response; and esreboxetine, a highly-selective norepinephrine reuptake inhibitor which plays a role in controlling the activity of this important neurotransmitter. These data will be presented at the 2008 American College of Rheumatology Scientific Meeting in San Francisco, California.

“Pfizer has an established track record of bringing innovative therapies to patients suffering with pain and inflammation,” said Martin Mackay, Ph.D., president, Pfizer Global Research and Development. “Data to be presented at ACR confirm our clinical approaches in developing these three compounds - CP-690,550, esreboxetine and tanezumab - as potential new medicines to provide relief from these serious medical conditions.”

Rheumatoid Arthritis
Data is being presented from several clinical trials studying CP-690,550, an oral medication that inhibits the Janus Kinase enzyme (JAK). This enzyme plays a major role in controlling the activation and proliferation of white blood cells, key elements of the immune system, which play a major role in rheumatoid arthritis (RA). CP-690,550 has shown encouraging results for the treatment of rheumatoid arthritis at doses that don't appear to be associated with excessive immune suppression.

Investigators will present interim results from a late-breaking Phase 2B study evaluating the activity of CP-690,550 in combination with methotrexate, the most commonly-used RA treatment. Approximately 60 percent of patients on doses at or above 3 mg of CP-690,550 responded to treatment as compared to 37.7 percent on placebo. These data confirm and extend the promising data seen in an earlier phase 2A study to this longer, 12 week study, and to patients who are already taking methotrexate to treat their rheumatoid arthritis.

Also being presented is a pharmacokinetic drug interaction study which showed that CP-690,550 and methotrexate can be co-administered without dose adjustment. In addition, preliminary results from an open label extension study will be presented.

In these studies, the most commonly reported adverse events were nausea, headache, dizziness, disorientation, hot flushes, urinary tract infections, diarrhea and liver function tests.

Larger and longer phase 3 studies are expected to start in 2009 to help further define the benefits and risks of CP-690,550 as a potential treatment for rheumatoid arthritis.
According to the Arthritis Foundation, 1.3 million Americans live with rheumatoid arthritis, a type of arthritis that can be severe, debilitating, deforming and even shorten life.

Osteoarthritis Pain
Pfizer continues to research new ways of treating osteoarthritis pain. Two studies to be presented highlight a new compound in development and new data for Celebrex (celecoxib) in the treatment of osteoarthritis pain.

Results from a Phase 2 study exploring the safety and efficacy of tanezumab, a novel biologic designed to block nerve growth factor, show that treatment once every eight weeks may significantly decrease pain in patients suffering from moderate to severe osteoarthritis pain in the knee. In the trial, approximately 75 percent of patients in both the tanezumab 100 and 200 mg/kg treatment groups experienced a 50 percent reduction in knee pain as compared to 26 percent of patients in the placebo group. In the study, the most common adverse events associated with tanezumab include headache, upper respiratory tract infection, paresthesia (abnormal sensations), hypoesthesia (decreased sensations) and arthralgia (joint aches).

Another late-breaking study evaluated continuous use of daily Celebrex treatment over a 22-week period compared to intermittent use of the medicine in preventing spontaneous OA flares. The study showed that continuous use resulted in 42 percent fewer OA flare episodes than the intermittent use. The results from the study also demonstrated that there were no significant differences in overall adverse events between the intermittent and continuous use groups.

According to the Arthritis Foundation, osteoarthritis affects 27 million Americans. Recent data show that one in two Americans are at risk for knee osteoarthritis over their lifetime. Loss of joint function as a result of osteoarthritis is a major cause of work disability.

Fibromyalgia
Pfizer is a pioneer in the study of fibromyalgia, investing many years of research into treatment options for this complex pain condition. In June 2007, Lyrica (pregabalin) CV became the first FDA-approved treatment for the management of fibromyalgia. Data supporting that approval showed Lyrica patients experienced significant reduction in pain as early as week one in some patients.

While widespread pain is the cornerstone of fibromyalgia, the condition is also characterized by other hallmark symptoms such as fatigue and difficulty concentrating.

Data presented at ACR will highlight the results of a phase 2 proof of concept study with esreboxetine, a highly selective norepinephrine reuptake inhibitor in a fibromyalgia population.

Data from this study showed that esreboxetine may be effective in relieving in key fibromyalgia symptoms, including pain, function and fatigue and was generally well tolerated. In the study, 43 percent of patients receiving esreboxetine reported their condition was much improved or very much improved as compared to 23 percent of placebo-treated patients.

The most common side effects compared to placebo were constipation, insomnia, dry mouth, headache and nausea. The proportion of patients who discontinued as a result of adverse events was 8.2 percent in the esreboxetine group and 2.3 percent in the placebo treatment group.

Fibromyalgia has been recognized by the professional community for over 30 years as a common, chronic widespread pain condition and is now thought to affect up to six million Americans. Recent evidence suggests a neurological basis to fibromyalgia, as demonstrated by brain scans and altered levels of certain neurotransmitters.