The tentative hypothesis that ezetimibe, by inhibiting absorption of dietary plant sterols in the Vytorin group in the SEAS trial, could promote the development and/or progression of cancer, has similar parallels to the recent University of Florida research reports on talc and its ability to stunt cancer growth.

When the hormone endostatin was first discovered in 1997, doctors hoped its tumor-fighting properties would lead to a cure for cancer. But clinical trials had been disappointing, possibly because most clinicians had injected the hormone directly into patients. The hormone breaks down in the body before it has a chance to slow the spread of cancer.

Scientists have only recently discovered that talc stunts tumor growth. The mineral has been used for almost 70 years to treat the respiratory problems that accompany metastatic lung cancer. About half of all patients accumulate fluid around the surface of the lungs, a condition known as malignant pleural effusion. That fluid can press down upon the lung, impair the breathing of the patient and cause the patient to feel very short of breath.

However, "thinking" scientists at UF have discovered that talc has the ability to stunt cancer growth by cutting the flow of blood to metastatic lung tumors. They revealed that the cells that cover the lining of the lung are stimulated by the presence of talc to produce a factor that inhibits the growth of blood vessels and kills the tumor cells themselves.

That "factor" was endostatin. The body produces 10-fold higher levels of endostatin, released by healthy lung cells. Endostatin prevents new blood vessels from forming, slows cell growth and movement, and even induces nearby tumor cells to commit suicide. All of these make it hard for tumors to grow and spread into healthy lung tissue.

But pharma-sponsored scientists thought they could develop another drug, patent it, get it a GoodHouseKeeping seal of approval and market it. But some scientist rethought the situation by understanding that by allowing talc in the chest cavity, thus constantly causing the normal cells to produce endostatin, inhibits the growth of tumors.

Again, the problem is that few scientific discoveries work the way we think and few physicians/scientists take the time to think through what it is they've discovered. This Vytorin/Zetia situation may be another case. I'm glad there are some physicians/scientists taking the time to think "outside the box."

Thanks, Gregory, that's interesting.

Here's our afternoon Vytorin update:
NEWS RELEASE
Committee on Energy and Commerce
Rep. John D. Dingell, Chairman

For Immediate Release: September 2, 2008
Contact: Jodi Seth or Alex Haurek, 202-225-5735

Dingell, Stupak Write Schering-Plough and Merck on
Vytorin-Cancer Link

Washington, D.C. – Reps. John D. Dingell (D-MI), the Chairman of the Committee on Energy and Commerce, and Bart Stupak (D-MI), the Chairman of the Oversight and Investigations Subcommittee, today wrote the Chief Executive Officers of Schering-Plough Corporation and Merck & Co., Inc. regarding a report the companies submitted to the Food and Drug Administration assessing Vytorin’s association with cancer.

The letter notes that the lawmakers have received the report, but “were somewhat surprised to discover that the report contains little more than the information that was presented at the July 21, 2008, press conference” announcing the report’s results. This comes after the Committee was informed by FDA that the report would provide “a complete assessment of Vytorin’s association with cancer.”

The letter asks when the report was prepared, whether the report provided to the Committee represents the totality of the information submitted to the FDA and why the report was not made publicly available.

The text of the letter is below.

September 2, 2008

Mr. Fred Hassan
Chairman and CEO
Schering-Plough Corporation
2000 Galloping Hill Road
Kenilworth, NJ 07033

Mr. Richard T. Clark
Chairman, President, and CEO
Merck & Co., Inc.
One Merck Drive
P.O. Box 100
Whitehouse Station, NJ 08889

Dear Mr. Hassan and Mr. Clark:

Under Rules X and XI of the Rules of the U.S. House of Representatives, the Committee on Energy and Commerce and its Subcommittee on Oversight and Investigations are continuing to investigate the safety and effectiveness of Vytorin, a prescription drug manufactured by Merck and Schering-Plough.

We have received a copy of Sir Richard Peto’s consultant report on the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study, which was submitted to the U.S. Food and Drug Administration (FDA). At our July 22, 2008, meeting with your counsel, we were advised that Dr. Peto’s report would provide a complete assessment of Vytorin’s association with cancer in the SEAS study and provide a full review of available data. After reviewing the five-page report, however, we were somewhat surprised to discover that the report contains little more than the information that was presented at the July 21, 2008, press conference announcing the SEAS results. We are also at a loss to understand why this report was kept by you from our Committee and the public.

We are concerned that an esteemed scientific consultant to Merck and Schering-Plough may have generated a secret report to FDA—a report whose contents may have been misrepresented to our staff as the report itself appears to contain information which is publicly available. Therefore, we ask that you provide answers to the following questions in writing:

1. Is the attached report the totality of Dr. Peto’s submission to FDA?
2. Why was Dr. Peto’s consultant study not made publicly available?
3. When did Merck, Schering-Plough, the Merck/Schering-Plough joint venture, or any of their agents, attorneys, or lobbyists first contact Dr. Peto about his consultant report?
4. When was Dr. Peto’s report submitted to FDA?
5. Was Dr. Peto’s report reviewed or edited prior to its submission to FDA by anyone from Merck, Schering-Plough, the Merck/Schering-Plough joint venture, or any of their agents, attorneys, or lobbyists? Please supply any drafts and all other documents that describe the review or editing of the report.
6. Has Dr. Peto prepared any other analysis of the association (or lack thereof) between Vytorin and cancer for any other regulatory agency or peer-review journal?
7. What role, if any, did Merck, Schering-Plough, the Merck/Schering-Plough joint venture, or any of their agents, attorneys, or lobbyists have in the preparation of the attached Peto report and decision to submit it to FDA?

Finally, we ask that you make Dr. Peto available for a staff interview as soon as possible.

Please deliver copies of your responses to the Subcommittee on Oversight and Investigations of the Committee on Energy and Commerce, Room 316, Ford House Office Building, no later than two weeks from the date of this letter. After review of your response, we may require additional records and/or staff interviews with company officials.

Thank you for your prompt attention to this matter.

Sincerely,

s/John D. Dingell s/Bart Stupak
Chairman Chairman
Committee on Energy and Commerce Subcommittee on Oversight and
Investigations

cc: The Honorable Joe Barton, Ranking Member
Committee on Energy and Commerce

The Honorable John Shimkus, Ranking Member
Subcommittee on Oversight and Investigations