Schering Plough, Merck: Potential Cancer Concerns

In a post on August 8^th, I advocated purchasing Schering Plough (SGP) and I spelled out my reasoning. In that post, I explained investor concerns of Vytorin. At that time, the ENHANCE panel found that Vytorin, a combination of Merck’s (MRK) Zocor and Schering’s Zetia, worked no better than Zocor alone at removing plaque from arteries. This information had the effect of reducing the market share of Vytorin from ~12% to about ~9.0%.

As if to add insult to injury, this week The New England Journal of Medicine contained three articles which came to the conclusion that patients taking Vytorin have an increased probability of cancer death. I will summarize the articles and try to forecast their impact on my predictions for SGP.

The first article’s findings (listing of SEAS trial data) 

• Aortic value replacement between those taking Vytorin vs. those on placebo was not statistically different
• Ischemic cardiovascular events in the Vytorin group were different than those taking placebo
• Last and probably most important, cancer deaths occurred more frequently in the Vytorin group vs. those in the placebo group (134 vs. 92)

The second article’s findings (editorial by Peto)

• Suggested that the cancer rates observed in the SEAS dataset were likely the result of an anomaly. He cites other large scale trials which include Vytorin such as:
  • SHARP (sample of 9,000 patients with follow up is 2.7 years)
  • IMPROVE-IT (sample of 11,000 with a follow up of 1.0 years) there is no overall excess of cancer and no significant excess at any particular site (sample of 20,000).
• He concluded cancer incidence appears to have been a numerical anomaly because the SEAS study has a sample of 1,800 individuals

The third article’s findings (editorial by Drazen)

• Discredits Peto’s SHARP and IMPROVE-IT findings because SGP and MRK provided funding for the SHARP and IMPROVE-IT studies
• Gastrointestinal cancers appeared higher in the Vytorin group:
  • Stomach cancers were 5 vs. 1 in the active vs. placebo group
  • Large bowel or intestine were 9 vs. 8
  • Liver, gallbladder, and pancreas 5 vs. 4
  • Skin cancer was 18 vs. 8
  • Lung cancer 7 vs. 10
  • Prostate 21 vs. 13
• Drazen concluded that physicians can not really know the safely or effectiveness of Vytorin

You can view the results of the study and the corresponding editorials here.

Clearly there is disagreement over the results but it is interesting to point out that:

• In the first 8-weeks of the SEAS study, LDL decreased by 61.3% to a mean level of 53mg/dL in the Vytorin group
• During the entire follow-up period, 53 months, Vytorin reduced mean LDL levels by 53.8% vs. 3.8% in the placebo group.

It is unclear what the total impact will be on the drug, SGP, or MRK. What is known is that there will likely be more media and political attention over the findings. I do not think that sales of drug will slow any more than they already have because the study seemed to prove that Cholesterol on average was lowered by a significant amount.

Disclosure: none

Comments

[johnnycanuck:]

The sales of Vyotrin could get hit allot more if the investigation by Reps. John Dingell and Bart Stupak, which are ongoing, turns up ANY discrepancies - whether with the drugs or the independence of the studies themselves. They being democrats and this being an election year though, what are the chances of that? Add to that the AHA issuing a statement on Tuesday reiterating that Vytorin should not be used as a first-line treatment but only when patients failed to respond to top doses of statins, and I believe the prescriptions will PLUMMET. Finally, I think the following statement does not bode well for MRK or SGP :
“The only place people should be taking it is in a clinical trial,” Dr. Allen J. Taylor of the Walter Reed Army Medical Center said of Zetia. www.nytimes.com/2008/0...

2008 Sep 03 06:03 PM

[generic int...:]

Too much information, released prematurely and mishandled by the media and many experts. Reminds me of the Avandia story, still awaiting data.

I guess we could conclude that Vytorin reduces the most common lung cancer death, prevents breast cancer death, yet increases cancer in general (stomach, skin and prostate) so that you are more likely dead within 3 years of taking a cholesterol lowering drug.

I don't think we have ever encountered a drug in the history of medicine that can kill a patient with cancers in multiple systems within three years. Why should Zetia do this? We don't even have a proposed mechanism, even though we are doing more cancer than cardiovascular clinical trials. I don't expect the NIH though, to start running trials for cancer prevention using drugs that increase cholesterol absorption.

The Seas trial was randomized for cardiovascular risk factors.....I doubt that it was randomized for cancer risk factors such as familial cancer tendency or prior personal history of cancer (other than identifiable active cancer which would exclude one from most clinical trials).

It seems irresponsible for the NEJM to advocate the science, but then selectively discard it, if associated with the pharmaceutical industry Many of our patients will only hear the false cry of cancer, and discontinue therapy inappropiately.

2008 Sep 03 10:59 PM