Your Vioxx Lawyer - Vioxx, Celebrex & Bextra FDA Transcript

Your Vioxx lawyer provides you the complete transcript of the February 16^th, 2005 joint meeting of the FDA's Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory Committee. We have formatted the complete transcript of the three day conference for easy of navigation to provide you with the best possible vioxx information. To contact a Vioxx Lawyer, click here for a FREE case evaluation.

NIH and Investigational Presentation: The PreSAP
Trial (Prevention of Colorectal Sporadic Adenomatous Polyps)

DR. LEVIN: Thank you very much, Dr. Hawk. Mr. Chairman, committee members, it is my honor to present a summary of the data in the PreSAP trial. My co-principal investigator, Dr. Nadir Arba, in Tel Aviv University, and I have been aligned with this trial since its birth with Searle, Pharmacia and Pfizer.

In this trial, depicted here are 1561 patients with sporadic adenomas who were randomized in a 3:2 manner and stratified by aspirin use and clinical center into celecoxib 400 mg daily for 36 months and placebo for 36 months. Colonoscopy was performed after 12 and 36 months of exposure evaluating recurrence, and collection of all pathological endoscopic information.

As you have already heard from Dr. Hawk, some of this information is still in a preliminary status. This study involved 106 clinical research sites in 32 countries. Patients were enrolled from March, 2001 and completed approximately one year later.

The cohort characteristics at baseline are shown in this slide, somewhat similar to the APC trial in terms of age and gender. What is different is that the smoking status is higher, 25 percent, and baseline aspirin use is lower. Some of this data may still be in a preliminary format so I am not going to discuss it significantly further.

Depicted here, and somewhat similar terms to that which Dr. Hawk showed, is the incidence and hazard ratio of the hierarchical cardiovascular composite endpoints. Again, the blue column that is highlighted reflects the death from cardiovascular causes--myocardial infarction, stroke or heart failure. I would draw to your attention the placebo rate of 6.4, approximately double that in the APC trial, and a hazard ratio of 1.1.

Similar to the APC trial, the cardiovascular events examined by baseline subgroups were somewhat similar in age, gender and baseline cardiovascular risk. There was no statistical evidence of a differential hazard ratio by baseline risk groups. Of course, there are few events and it has limited power.

Depicted here on this Kaplan-Meier estimate, one can see that the number of events is low, and when this is magnified, similar to what Dr. Hawk showed, the curves are essentially similar.

There are a number of issues which arise from these two trials. Perhaps the most important one which concerns us as the investigators, apart from the safety, is the efficacy and we don't have that information yet. We have some idea with the signal from the Vioxx trial about which you heard earlier. It is tantalizing. That will help us to make risk/benefit assessments for future.

We have to take into consideration in any of those discussions the relative gastrointestinal and cardiovascular safety referent to other non-steroidal anti-inflammatory drugs. Overall toxicity and safety, of course, are prime concerns when it comes to asymptomatic individuals and the public, and we don't have any information in these trials yet on gastrointestinal ulceration. The cross trials meta-analysis that Dr. Hawk alluded to will also provide a great deal of information. What, of course, is most tantalizing to everyone involved is why is there a difference in this trial compared to the APC trial? At this point, all we have to go on is the frequency or the schedule of administration of celecoxib. We don't have any other information from the patients enrolled in this trial on other possible factors.

In this trial there was no increased risk of cardiovascular adverse effects, but one overall would want to consider whether one could mitigate any increased risk by better clinical management if that were necessary.

Some of the differences, but that doesn't really apply to this trial, might be in metabolic polymorphisms but there is no evidence for that and we don't have that information.

So, for future research there are many questions that are of great importance. COX-2 remains a relevant oncology target and, as Dr. Hawk already presented, we want to consider the possibilities that there are other pharmacological targets besides COX-2 in the prevention and therapy of cancer. We already have some information on that, the effect of these agents, and they don't all do the same, on 15-lipoxygenase-1 and also on the modulation of PPOD delta.

But primarily what we are interested in now is establishing efficacy or determining efficacy in these two trials and that information should be forthcoming in the next few months. Thank you for your attention.

Weitz & Luxenberg is no longer accepting Vioxx cases.

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