WASHINGTON - Pivotal Phase III studies of Monsanto Co.'s new non-steroidal anti-inflammatory drug (NSAID), Celebrex, indicate the compound works as well as commonly prescribed NSAIDs in relieving the signs and symptoms of rheumatoid arthritis (RA), but without gastrointestinal side effects.
Celebrex (celecoxib), one of a new class of NSAIDs, is currently under priority review at FDA and will be the first of this new class of drugs to be considered by the agency's Arthritis Advisory Committee, on Dec. 1.
"We think this is a drug that has real benefit and meets and unmet medical need at the moment," said Nancy Tait, spokeswoman for G.D. Searle, the pharmaceutical division of St. Louis-based Monsanto. "And, assuming we do eventually get approval, we are prepared to have it on the market very quickly."
Tait said the company anticipates approval in the first or second quarter of 1999.
Prostaglandins are the main perpetrators of the pain in inflammation. Normally, these ubiquitous substances carry out housekeeping duties all over the body. When disease or trauma triggers inflammation, the body produces a flood of prostaglandins.
All NSAIDs ease pain and inflammation by inhibiting the enzymes that create prostaglandins from the fatty acid arachidonic acid. However, currently approved NSAIDs indiscriminately block both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2).
Present in most human tissues, COX-1 is vital to protecting the gastrointestinal (GI) system, and to maintaining normal platelet and kidney function. COX-2, on the other hand, is turned on in response to inflammation. Blocking COX-1 can lead to gastrointestinal ulceration and bleeding, inhibition of platelet aggregation and dangerous interactions with other drugs.
Upper gastrointestinal complications from NSAID use currently result in 107,000 hospitalizations and 16,500 deaths each year in the U.S. Unlike currently approved NSAIDs, Celebrex selectively blocks COX-2, allowing COX-1 to continue to function normally and thus reducing potentially dangerous side effects. These results come from four Phase III studies presented at a meeting of the American College of Rheumatology, in San Diego.
Celebrex Causes Fewer GI Problems Than Naproxen
A 12-week study involving 1,149 RA patients suffering flares demonstrated Celebrex was as effective as the commonly used NSAID naproxen in relieving joint pain and swelling. Celebrex, however, caused significantly fewer gastrointestinal problems. A 12-week study of 1,004 patients with osteoarthritis showed similar results.
A 24-week study of the drug in 600 RA patients showed that it worked as well as the NSAID diclofenac, but resulted in a four-fold decrease in ulcers that could be detected with endoscopy. In addition, far fewer patients receiving Celebrex dropped out of the study due to GI complaints.
Celebrex also proved compatible with two medications commonly prescribed to arthritis patients: methotrexate for the treatment of RA; and warfarin, a blood thinner prescribed for concomitant cardiovascular conditions, such as blood clots.
"It's like the old science brought us some great drugs, but they had some serious side effects," said Tait. "With the advances in molecular biology and screening, it lets the scientist specifically target a drug so you don't get all the collateral damage."
Searle and Pfizer Inc., of New York, will develop and commercialize Celebrex in all world areas except Japan, where Searle will develop the drug with Yamanouchi Pharmaceutical Co., of Tokyo.
Celebrex is also being studied in clinical trials for the treatment of Alzheimer's disease and prevention of colon cancer.
Monsanto's stock (NYSE:MTC) closed Friday at $38.562, up $0.562. Pfizer's stock (NYSE:PFE) ended the day at $105.375, up $1.062. n