This article is part of the Arthritis Archives.
Editor note: "Celebra" later named Celebrex was FDA approved in December 1998. Vioxx was FDA approved in May 1999. On 09/30/2004, Merck the maker of Vioxx, issued a worldwide recall, halting sales of the drug. On 04/07/2005, Following scrutiny of the class of arthritis drugs known as NSAIDs and COX-2 inhibitors, the FDA announced planned regulatory actions. See: Questions & Answers: FDA Actions On COX-2 Inhibitors & NSAIDs Fallout from the Vioxx recall will continue for years to come.
Dateline: June 23, 1998
COX-2 Selective Inhibitors New "Super Aspirins"
An arsenal of anti-inflammatory drugs has been used to treat arthritis for many years. Current and ongoing research is striving to develop more effective and safer drugs. Scientists are about to make an exciting breakthrough with a whole new class of arthritis medications known as COX-2 selective inhibitors.
Pain, redness, heat, and swelling, which are the markers of inflammation, follow the release of prostaglandins. Aspirin and similar nonsteroidal anti-inflammatory drugs (NSAIDS) reduce prostaglandins by blocking an enzyme which helps to produce them, called cyclooxygenase (COX).
NSAIDS are among the most heavily used drugs in the world, even though they have been disappointing in their benefits and ridden with side effects. Last year, seventy-seven million prescriptions for NSAIDS were written in the United States. In the United States alone, NSAIDS account for sales of as much as eight billion dollars a year. They have been hugely popular because until now they were considered the best alternative to higher risk immunosuppressant therapies used to treat disabling types of arthritis. Yet most people who use NSAIDS have eagerly awaited something better which would promise more relief and which would abate the unwanted side effects.
Currently, a number of powerful drugs are in clinical testing. There is one compound, exulted as a "Super Aspirin" which has turned everyone's head and has renewed hope among both arthritis sufferers and researchers. So far, more than ten thousand people have tried it and none have experienced any serious side effects.
Phillip Needleman, the researcher responsible for the "Super Aspirin" credits its discovery to a rabbit's kidney which he was studying years ago when he was the chairman of the pharmacology department at Washington University in St. Louis. From his research he hypothesized there were two kinds of COX enzyme. One COX enzyme provided regular levels of prostaglandin which kept the stomach, platelets, kidneys, and other tissues in working order. The second COX enzyme was produced only in the event of inflammation or trauma and generated the high levels of prostaglandins which cause inflammation.
In 1990, at an international conference, Needleman predicted that two such forms of COX would be found and that blocking COX-2 would selectively control inflammation yet not disturb physiology. Shortly thereafter, other scientists confirmed his hypothesis and isolated the second enzyme. Needleman then directed his efforts to find a drug which could distinguish between the two COX enzymes.
Since 1991, Needleman has been the chief scientist at Monsanto Company. Needleman, along with all the medicinal chemists at Monsanto, worked to clone the gene for COX-2 and prepared a large amount of the enzyme, reviewed known NSAIDS and their chemical structures while speculating their affinity for COX-1 or COX-2, and eventually created a chemical backbone refined into a compound called celecoxib which blocked COX-2 yet spared COX-1. Studies of celecoxib advanced from test tube to animals to man. In March 1995, five years after Needleman presented his theories at the international conference, the first patient was treated with this new drug which Monsanto has named Celebra. Editor note: The name "Celebra" was later changed to Celebrex.
The potential for Celebra in terms of reduced inflammation, symptomatic pain relief, and possibly even modifying the underlying disease has swelled the expectations of those awaiting the drug's release. The potential market for COX-2 inhibitors is enormous with projected sales of up to five billion dollars a year in the United States. Monsanto is seeking initial FDA approval only for the treatment of arthritis, although its potential use for other conditions such as cancer and Alzheimer's disease has also been touted.
Merck has also completed advanced clinical trials of a COX-2 inhibitor. The Merck version is known as Vioxx. It is expected that Celebra and Vioxx will be available in less than two years. A whole new category of drugs inciting a whole new wave of optimism and hope.
Source: The New Yorker, June 15, 1998 "Super Aspirin", by Jerome Groopman
First published: 06/23/1998