Category Archives: Merck Schering Q2 Form 10-Q SEC Hassan Clark JV Termina

Merck’s reaction to SEAS (v. Schering’s), each as filed with the SEC. . . .

When Merck recently filed its Form 10-Q with the SEC, it had this to say about SEAS:

. . . .On July 21, 2008, efficacy and safety results from the Simvastatin and Ezetimibe in Aortic Stenosis (“SEAS”) study were announced. SEAS was designed to evaluate whether intensive lipid lowering with Vytorin (ezetimibe/simvastatin) 10/40mg would reduce the need for aortic valve replacement and the risk of cardiovascular morbidity and mortality versus placebo in patients with asymptomatic mild to moderate aortic stenosis who had no indication for statin therapy. Vytorin failed to meet its primary end point for the reduction of major cardiovascular events. There also was no significant difference in the key secondary end point of aortic valve events; however, there was a reduction in the group of patients taking Vytorin compared to placebo in the key secondary end point of ischemic cardiovascular events. Vytorin is not indicated for the treatment of aortic stenosis. Vytorin contains two active ingredients: ezetimibe and simvastatin. No incremental benefit of Vytorin on cardiovascular morbidity and mortality over and above that demonstrated for simvastatin has been established. In the study, patients in the group who took Vytorin 10/40 mg had a higher incidence of cancer than the group who took placebo. There was also a nonsignificant increase in deaths from cancer in patients in the group who took Vytorin versus those who took placebo. Cancer and cancer deaths were distributed across all major organ systems. The Company believes the cancer finding in SEAS is likely to be an anomaly that, taken in light of all the available data, does not support an association with Vytorin. The Company, through its joint venture, is committed to working with regulatory agencies to further evaluate the available data and interpretations of those data; however, the Company does not believe that changes in the clinical use of Vytorin are warranted.

In light of the announcement of the SEAS results, the Company intends to monitor sales of Vytorin and Zetia. . . .

[Emphasis supplied.]

Now compare that, to what Schering-Plough had to say — about the very same study, it its own Form 10-Q — about that study’s potential effects upon Schering’s operations and prospects. Remember now that Merck is nearly one-and-one-half times Schering’s size, on the total assets line. What gives? What could explain such wildly differing assessments — especially given that in SEC filings, in each case, all material information as to any material matter — free of any material omission — is required by the applicable federal securities rules?

. . . .SEAS Clinical Trial.

On July 21, 2008, preliminary results of the Merck/Schering-Plough cholesterol joint venture’s SEAS (Simvastatin and Ezetimibe in Aortic Stenosis) clinical trial, in which VYTORIN was studied for a new potential use, its effect on patients with aortic stenosis, and no evidence of cardiovascular disease, were released to the public. The results showed that, although VYTORIN reduced LDL-cholesterol by an average of 61% compared to placebo; there was no significant difference between VYTORIN and placebo on the primary endpoint which was a combination of the occurrence of aortic valve replacement surgery and major cardiovascular events. Currently, valve replacement surgery is the treatment of choice for aortic stenosis. However, the results did show VYTORIN was significantly more effective than placebo in reducing the incidence of atherosclerotic events. In addition, although VYTORIN was generally well tolerated by patients in the clinical trial, there was an imbalance in the occurrence of cancer between the treatment and placebo arms, with a higher incidence and a higher number of cancer deaths in the VYTORIN arm.

Because the cancer data from the SEAS clinical trial involve only 158 patients, the higher cancer incidence may be a result of chance and not attributable to VYTORIN. Accordingly, to better understand the possible implications of these unexpected cancer data, the University of Oxford Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU) performed an independent analysis of the combined cancer results from two other, ongoing studies involving VYTORIN. The SHARP (Study of Heart and Renal Protection) clinical trial, is a randomized, placebo-controlled trial of VYTORIN in 9,400 patients with chronic kidney disease. The other clinical trial, IMPROVE-IT (Examining Outcomes in Subjects With Acute Coronary Syndrome:Vytorin (Ezetimibe/Simvastatin) vs Simvastatin), is a randomized, double-blind trial of VYTORIN compared to simvastatin alone in patients with acute coronary disease. Currently, there are 12,000 patients enrolled in the IMPROVE-IT clinical trial, with a total planned enrollment of 18,000. The SEAS clinical trial, by contrast, included 1,873 patients. CTSU worked independently of Schering-Plough, Merck and the Merck/Schering-Plough cholesterol joint venture to perform the analysis.

CTSU found that in the SHARP and IMPROVE-IT clinical trials, there was not the cancer imbalance observed in the SEAS clinical trial. Cancers in the SHARP and IMPROVE-IT clinical trials were distributed equally across all treatment arms and showed no clustering of any cancer type. The cancers observed in the SEAS clinical trial were also not clustered, that is they were distributed across all major organ systems. Also, the incidence of cancers was consistent with the rates that would be expected based upon data from Scandinavian age-adjusted cancer registries. Further, there was no year-by-year increase in cancer rates as would be expected where a compound increases cancer risk. Having reviewed all of the available data, the CTSU concluded that the SEAS, SHARP, and IMPROVE-IT clinical trials “do not provide credible evidence of any adverse effect on cancer”. Schering-Plough believes the cancer finding in SEAS is likely to be an anomaly that, taken in light of all the available data, does not support an association with VYTORIN. Schering-Plough, through the Merck/Schering-Plough cholesterol joint venture, is committed to working with regulatory agencies to further evaluate the available data and interpretations of those data; however, Schering-Plough does not believe that changes in the clinical use of VYTORIN are warranted. . . .

[Emphasis supplied.]

First, quickly, here — does this mean Schering-Plough is not going to monitor the SEAS subjects for cancer, longitudinally? Only Merck will? What? That can’t be right.

Next, and perhaps more importantly — it is entirely unclear to me what Schering was trying to say — or intended to say — with this bit, from the above: “. . . .do not provide credible evidence of any adverse effect on cancer. . . .” What exactly is an “adverse affect on cancer“?

Does this form of parsing intend to simply suggest that Vytorin will not, in the opinion of the doctor at CTSU, make existing cancers worse? If that is what was intended, then what remains unsaid — is rather troubling. What remains unsaid, then, is that “there can be no assurance that Vytorin did not contribute to the appearance of cancers, in previously-unafflicted subjects, enrolled in the treatment arm of the SEAS study. . . .”

Finally, it is puzzling to me that Merck has filed the full-text of all the recently-amended Worldwide Cholesterol Joint Venture agreements as “material contract” exhibits to its Form 10-Q, and Schering (again, at not quite two-thirds the size of Merck — in total assets) has omitted them. It simply cannot be that these amendments and agreements are “immaterial” to Schering. Again, what gives? Did the SEC sign-off on a single filing of the agreements, allowing Schering to omit them from its filing?

That would be highly unusual, in my experience — as Merck and Schering are not generally affiliates of one another, in the language of the SEC. Only their Cholesterol Joint Venture is an “affiliated person” of each of them. So, again, what gives?

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