By Lisa Seachrist
WASHINGTON - The FDA has given the nod to Monsanto Co.'s new non-steroidal anti-inflammatory drug (NSAID), Celebrex (celecoxib), to treat the signs and symptoms of arthritis, without serious gastrointestinal side effects.
The agency approved the drug last Thursday as a treatment for both osteoarthritis and rheumatoid arthritis. Celebrex will retain the warning about gastrointestinal side effects that accompanies the labels of all NSAIDs, until the results of post-marketing studies show that the warning is unnecessary. Nevertheless, St. Louis-based Monsanto heralded Celebrex's approval as an endorsement for "smart" drug development.
"It is a very exciting day for us," said Richard De Schutter, co-president of G.D. Searle, Monsanto's pharmaceutical division, and vice chairman of Monsanto. "We see this as an event of enormous importance."
Celebrex, like all NSAIDs, works by blocking the production of prostaglandins that cause the pain associated with inflammation. NSAIDs inhibit the enzymes (cyclooxygenases) that create prostaglandins from arachidonic acid. Unfortunately, in blocking the production of prostaglandins, NSAIDs as a class can lead to stomach ulceration and perforation.
Celebrex differs from other NSAIDs, such as ibuprofen and naproxen sodium, by specifically blocking cyclooxygenase-2 (COX-2), leaving COX-1 to protect the gastrointestinal system and maintain normal platelet activity.
Monsanto developed the COX-2-inhibiting Celebrex with the idea that blocking COX-1 can lead to ulceration and bleeding, inhibition of platelet aggregation, and dangerous interactions with other drugs. The company had requested that the agency drop the NSAID warning, based on studies which showed that patients taking Celebrex had a much lower incidence of endoscopically diagnosed gastrointestinal ulcers than patients on other NSAIDs.
The agency, however, declined to remove the label, noting that these sorts of ulcers can resolve on their own and that the company failed to establish an annual event rate for ulceration and bleeding.
"We knew what was expected to remove the NSAID warning - a very large clinical trial," said Philip Needleman, co-president of Searle. "In well over 5000 patients on Celebrex, only two had significant upper [gastrointestinal] bleeds. Based on this, we agreed to move on and complete future trials."
Monsanto has already established two very large post-marketing studies to demonstrate Celebrex's ability to reduce arthritis pain without the gastrointestinal side effects.
The company will begin shipping the drug in 10 days and expects it to be available in more than 32,000 pharmacies by Jan. 25. In addition, the company will offer an early-experience program to a number of physicians and their patients, under which patients will be supplied with a free, 25-day supply of the drug, while the company supplies pharmacies throughout the U.S. by mid-February.
Monsanto has priced the drug with an eye to aggressively challenging current branded NSAIDs. The 100-milligram capsule will bear an average wholesale price of $1.43, and the more commonly prescribed 200-milligram capsule's average wholesale price will be $2.42.
"We had a number of goals when developing Celebrex," said Al Heller, chief operating officer for Searle. "First and foremost, we hit our therapeutic goal. Another goal of ours was to be socially responsible in pricing the drug. At $2.42 a day, Celebrex is priced as low or lower than all of the common branded NSAIDs."
Pfizer Inc., of New York, will market the product in the U.S., in conjunction with Searle. Pfizer will develop the drug elsewhere in the world except in Japan, where Searle will develop the drug with Yamanouchi Pharmaceutical Corp. Ltd., of Tokyo.
Monsanto's stock (NYSE:MTC) closed Monday at $47.937, up $0.437. n