An analysis of cancer data from three trials evaluating Schering-Plough's Zetia (ezetimibe) may help quell concerns arising from a cancer safety signal seen in preliminary results from the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial.

Researchers from Oxford University compared the SEAS data with interim cancer data from the SHARP and IMPROVE-IT trials and said they failed to find "credible evidence of any adverse effect of ezetimibe on rates of cancer."

The review was triggered by data from the SEAS trial, where patients receiving Vytorin showed a statistically significant increase in cancer incidence compared to placebo. The analysis appears in the Sept. 25 New England Journal of Medicine.

The investigators held a press conference July 21 to release top-line results from their analysis (¹ Also see "Cancer Signal Triggers Vytorin Study Review" - Pink Sheet, 21 July, 2008.).

Vytorin combines Merck & Co.' s Zocor (simvastatin) and Zetia into a lipid-lowering combination drug.

The analysis found a nonsignificant increase in deaths from cancer when combining data from the three trials, but the researchers argue that a real increase in cancer-related mortality should be accompanied by an increase in cancer rates.

In an accompanying editorial, Jeffrey Drazen, Harvard University, et al. caution, "the fact that the combined data from all three trials showed an increase in cancer mortality with ezetimibe should not be assumed to be a chance finding until further data are in."

Full results of SEAS data are scheduled to be released Sept. 2 at the European Society of Cardiology meeting, and could provide critics another opportunity to question the safety of the combination product.

Indeed, the data release "could once again culminate in lots of nasty headlines [particularly] if critics like Dr. Steve Nissen become involved," Bernstein analyst Tim Anderson writes in an Aug. 29 report.

"History suggests that Dr. Nissen, or a small number of others that share his views, may mount another concerted attack at or around the time that the SEAS data gets released next week," Anderson says.

Members of Congress, state legislators and the scientific community - including Nissen - have scrutinized Merck and Schering since it was revealed in May that the firms withheld unfavorable results of the ENHANCE trial for nearly two years after the trial was completed. The study showed Vytorin had no significant benefit over simvastatin alone in atherosclerosis prevention ² Also see "States Subpoena Schering-Plough For Vytorin Documents" - Pink Sheet, 7 May, 2008.).

-Brian Marson (b.marson@elsevier.com)

New Look At Ezetimibe Fails To Confirm Vytorin Cancer Signal

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