Two trials for the COX-2 inhibitor Celebrex in prevention of adenomatous polyps take on added significance following Merck's withdrawal of Vioxx .

Pfizer said Oct. 1 that the trials "have not shown any significant safety issues and are expected to continue to completion."

The first study, a 2,000 patient trial conducted by the National Cancer Institute, has three arms: 400 mg twice daily, 200 mg twice daily, and placebo. Nine hundred and thirty patients have reached the 36-month plateau.

Pfizer is conducting the second study, a 1,500 patient trial comparing 400 mg once daily to placebo. Currently, 325 patients have reached the three-year threshold.

An external steering committee meets every six months to examine preliminary data for safety risk, the company said.

Since the trial protocols call for both studies to be followed out for five years, data will not be available for another two years, Pfizer said.

Pfizer's statement suggests that it feels the ongoing studies are sufficient to satisfy FDA's expected request for long-term studies. After Merck announced the withdrawal of Vioxx, FDA indicated it would request long-term data for COX-2s (see ¹ Also see "COX-2 Market Growth Could Be Stalled Until Release Of Long-Term Safety Data" - Pink Sheet, 4 October, 2004.).

The design of the Pfizer trials appears similar enough to the Vioxx trial to allow for some comparison.

In Merck's 2,600-patient APPROVe (Adenomatous Polyp Prevention on Vioxx) trial, patients were randomized to Vioxx or placebo.

During the first 18 months of continuous treatment, patients receiving Vioxx exhibited the same rate of cardiovascular adverse events as patients receiving placebo (0.375%).

However, after 36 months of treatment, Vioxx patients exhibited twice as many cardiovascular adverse events as those on placebo (1.5% for Vioxx vs. 0.75% for placebo). There were five fatal cardiovascular adverse events in each arm during the three-year trial.

Celebrex was granted accelerated approval for the treatment of familial adenomatous polyposis Dec. 23, 1999 based on the surrogate endpoint of mean percentage change in number of rectal polyps (² Also see "Celebrex FAP Study Will Explore Delay Of Surgery In Pediatric Patients" - Pink Sheet, 20 December, 1999., p. 5).

Pfizer has committed to a confirmatory placebo-controlled study as well as long-term registry in FAP patients which would compare outcomes and adverse events to untreated historical controls.

Pfizer Celebrex Polyp Trials Get Added Weight With Vioxx Withdrawal

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