Vytorin Gets Medical Group Support, Congressional Query On ENHANCE

Merck/Schering-Plough's Vytorin has drawn support from major medical groups as it faces a new Congressional inquiry and possible legal action in the wake of unfavorable study results from the much-anticipated ENHANCE trial.

Results released by the companies Jan. 14 show the ezetimibe/simvastatin combination therapy failed to demonstrate significant benefit compared with simvastatin alone in preventing formation of arterial plaque.

The findings confirmed months of speculation, fueled by repeated delays in reporting the data, that the trial would fail to show an edge for the combination drug over simvastatin.

Medical Groups Reassure Patients

In response to the report, three major cardiovascular medical groups issued statements Jan. 15 aimed at reassuring patients taking Vytorin.

The American Heart Association, American College of Cardiology and National Lipid Association urged caution in interpreting results and discouraged patients from discontinuing Vytorin without first consulting with their physician.

The groups pointed to limitations of the ENHANCE study design and noted that three other studies, including IMPROVE-IT, are evaluating cardiovascular endpoints.

The ACC recommended that "major clinical decisions not be made on the basis of the ENHANCE study alone." The group added "this is not an urgent situation" and "further research will be needed in this area to provide conclusive evidence about which lipid lowering strategy is preferred."

Similarly, AHA emphasized that "the study was not large enough or long enough to determine whether the combination drug is more or less effective than the single drug in reducing heart attacks or deaths."

The announcement could impact sales of Vytorin, which has continued to gain market share despite the availability of generic simvastatin (¹ (Also see "Generic Simvastatin No Heartache For Crestor Or Vytorin" - Pink Sheet, 30 Jul, 2007.), p. 16). Vytorin's share stands at 12.2 percent of the U.S. statin market.

However, a possible sales hit is not the only challenge ahead for Merck and Schering-Plough. The companies face a Congressional inquiry and a legal challenge over their handling of the trial data and marketing tactics.

Reps. John Dingell, chairman of the Energy and Commerce Committee, and Bart Stupak, chairman of the Oversight and Investigations Subcommittee, sent Jan. 16 letters to the companies questioning their failure to release the ENHANCE data while running direct-to-consumer ads for Vytorin.

The letters also express concern that the study's primary investigator was not included in an outside advisory panel set up to provide expertise on dealing with the trial data, nor was he present when the panel recommended altering the study's endpoints.

The Democratic representatives sent a separate letter to FDA Commissioner Andrew von Eschenbach requesting records relating to the ads.

The holdup in the public release of the study results, completed in April 2006, prompted an inquiry from the House Energy and Commerce Committee in December 2007. The panel requested details on the trial and implied that the delay may be linked to data manipulation (² 'The Pink Sheet' Dec. 17, 2007 In Brief).

Merck and Schering-Plough, however, attributed the delay to the rigorous trial design and analytical process.

Vytorin Not Enhanced By Study Data

The ENHANCE (Effect of Combination Ezetimibe and High-Dose Simvastatin vs. Simvastatin Alone on the Atherosclerotic Process in Patients with Heterozygous Familial Hypercholesterolemia) trial evaluated the highest dose of Vytorin (10 mg ezetimibe plus 80 mg simvastatin) versus 80 mg simvastatin in 720 patients with a rare condition that leads to extremely high LDL cholesterol.

The study found "no statistically significant differences between treatment groups" in either the primary endpoint of mean change in the intima-media thickness or in key secondary imaging endpoints. Overall incidence of treatment-related adverse events was generally similar between the two groups.

The companies had planned to release results at the upcoming American College of Cardiology meeting in late March but decided to do so earlier in the interest of transparency and in response to intense interest in the trial, Schering-Plough told "The Pink Sheet." However, the firms still expect a discussion of the results at ACC.

During recent presentations to the investment community, executives at Merck and Schering-Plough downplayed the relevance of ENHANCE to the value of Vytorin (³ (Also see "Can ENHANCE Diminish Vytorin? Schering, Merck Minimize Trial’s Importance" - Pink Sheet, 7 Jan, 2008.), p. 3). Results of the ongoing 10,000-patient IMPROVE-IT trial, evaluating Vytorin in acute coronary syndromes, are expected to be more definitive in determining outcomes, they claim. IMPROVE-IT results are due by 2011.

The firms also emphasized what they consider to be Vytorin's key attribute: superiority over simvastatin in reducing LDL cholesterol. Vytorin significantly reduced LDL levels by 58 percent in the ENHANCE trial, compared with a 41 percent decrease in the simvastatin group after 24 months.

Vytorin, Zetia Marketing Challenged In Court

Separately, prominent plaintiffs firm Hagens Berman Sobol Shapiro filed a proposed class action lawsuit Jan. 17 alleging the two companies violated state consumer protection laws in the sale and marketing of Vytorin and Zetia (ezetimibe). The complaint was filed in U.S. District Court in Seattle.

The suit claims the companies have known since 2006 that the combination of drugs was no more effective than simvastatin in reducing arterial plaque, yet delayed releasing the findings and did not change their marketing approach for the drugs.

Hagens Berman has a track record pursuing litigation against drug companies over their marketing and sales campaigns.

The firm represents a former Pfizer employee in a whistleblower suit alleging the company boosted Lipitor sales through off-label marketing and promotion. The firm also represents labor and consumer groups in a pending case against First DataBank and McKesson over their average wholesale price reporting.

- Cathy Kelly ([email protected])