January 25, 2008 (Washington, DC) – More than 10 days since results of the ENHANCE trial were made public in a press release issued by Merck/Schering-Plough Pharmaceuticals, the makers of the ezetimibe and simvastatin cholesterol-lowering combination (Vytorin), the drug remains in the spotlight. This time, however, the companies, as well as the American Heart Association (AHA) and the American College of Cardiology (ACC), are in the sights of the media and government oversight committees.
Yesterday, the US House Committee on Energy and Commerce sent letters to the AHA, the ACC, and to Merck/Schering-Plough Pharmaceuticals, asking about their financial arrangements. Both the AHA and ACC have come under fire for statements issued in the wake of the release of the ENHANCE study findings, statements that urged patients not to panic about the findings and that clinical decisions not be made based on the data of this surrogate-end-point trial.
"Conclusions should not be made until the three large clinical-outcome trials are presented within the next two to three years," read the January 15, 2008 ACC press release. "The ACC recommends that Zetia [ezetimibe] remain a reasonable option for patients who are currently on a high-dose statin but have not reached their goal. The ACC also notes that Zetia is a reasonable option for patients who cannot tolerate statins or can tolerate only a low-dose statin."
The AHA issued a similar statement a day after ENHANCE was released, telling the public the study was too limited and not designed to draw conclusions about the drug's ability to reduce hard clinical end points. The AHA advised patients not to stop the drug without talking to their doctors.
Where the AHA and ACC have drawn fire is in the funding both receive from industry. In their statement, the AHA failed to disclose that it receives $2 million annually from Merck/Schering-Plough, the joint venture that funded the study and currently markets the ezetimibe/simvastatin combination. In addition, a link from the AHA website to external sites did not make explicitly clear that these external sites were sponsored by large contributions from Merck/Schering-Plough and other drug companies. The AHA has since changed the site to make the sponsorship of these companies clear.
Rumors and innuendo
With the release of so much of the ENHANCE data on January 14, 2008, there are questions surrounding the presentation of the study results at the upcoming ACC Scientific Sessions in Chicago, IL, this March. Specifically, there are issues related to embargo and whether or not Merck/Schering-Plough broke the embargo with the release of data to the public prior to their scheduled presentation at the ACC meeting.
Amy Murphy, associate director of media relations with the ACC, told heartwire that no decision has yet been made with regards to ENHANCE. There will be discussions with the late-breaking clinical-trials' cochairs, along with ACC president Dr James Dove, about the placement of the study within the meeting. She suspects the study will not be included in the late-breaking clinical-trials session but presented at the meeting in a different forum.
More information on the fate of ENHANCE at the ACC will follow as available.
Today, the US Food and Drug Administration issued an early communication regarding its ongoing review of Vytorin and the ENHANCE trial. The agency said it would continue to review the data to determine what course of action to take with the drug. The report is expected to take about six months. At present, the FDA said it does not yet have the full results of the ENHANCE trial.
Drawing the ire of the House
The Energy and Commerce Committee, according to documents obtained by the Wall Street Journal, is interested in whether or not the ACC urged Merck/Schering-Plough to release the ENHANCE results, an issue that came to light when the company was criticized for not presenting the results sooner . The committee also wants to know the names of the doctors responsible for drafting the ACC statement.
Both the AHA and ACC deny that funding from Merck/Schering-Plough had anything to do with the press releases issued after the ENHANCE data were made public. Dr Daniel Jones (University of Mississippi Medical Center, Jackson), president of the AHA, told the New York Times that the association does not list industry funding when issuing statements for patients .
Last night, in a request from heartwire , the ACC issued a statement: "The American College of Cardiology is in receipt of the letters from the Senate Finance Committee and the House Committee on Energy and Commerce regarding our January 15, 2008 statement on the release of the ENHANCE trial results. The ACC appreciates the committees' acknowledgement of the college's long-standing reputation as being objective, impartial, and trusted by patients and doctors alike. The ACC will comply with all congressional requests for information related to the January 15 statement."
More Vytorin news . . .
Merck/Schering-Plough have suspended their ubiquitous Vytorin television advertisements, although they will continue to run print ads. According to company officials, the television ads have been suspended because of the "misinterpretation" of the ENHANCE results. Not coincidentally, US Congress is now poking its nose into the marketing of Vytorin and the $102 million the companies spent to market the drug in 2007.
In a letter to the FDA, Congress is "concerned that the study's results may have been available to Schering-Plough and Merck officials and yet the massive advertisement campaign for Vytorin was allowed to continue."
It is also investigating whether the companies withheld the ENHANCE data and used misleading statements in their advertisements. And finally, Congress is pressing Merck/Schering-Plough for information on the timing of executive stock sales, specifically sales that might have occurred during a delay in the release of the results.
Today, the companies issued a press release responding to "mischaracterizations" about the ENHANCE trial, particularly the delay in presenting the data .
"While the ENHANCE trial was time-consuming and took longer than originally anticipated to complete, our companies acted with integrity and good faith in connection with the trial," Dr Thomas Koestler, president of the Schering-Plough Research Institute, is quoted in the release. "We took numerous actions to ensure the quality of the reading of the ultrasound images."
The companies state they look forward to "participating in rigorous scientific debates" about Vytorin, noting that the ENHANCE study is expected to be presented at the ACC meeting in March.
In addition to the press statement, the companies issued a five-page chronology of the ENHANCE trial, beginning in late 2000 when the protocol for the trial was first discussed and concluding in January 2008 with the submission of a late-breaker place-holder abstract for the ACC meeting .
Goldstein J. Vytoringate! Senate boards bandwagon. Wall Street Journal Health Blog, January 24, 2008. Available at: https://www.wsj.com .
Saul S. Heart group backs drug made by ally. New York Times, January 24, 2008. Available at: https://www.nytimes.com .
Merck/Schering-Plough. Merck and Schering-Plough respond to issues raised about ENHANCE clinical trial [press release]. January 25, 2008. Available at: https://www.sch-plough.com/schering_plough/news/release.jsp?releaseID=1100091 .
Merck/Schering-Plough. ENHANCE Chronology. January 25, 2008. Available at: https://media.corporate-ir.net/media_files/IROL/89/89839/ENHANCE_Chronology_012508.pdf .
The complete contents of Heartwire , a professional news service of WebMD, can be found at www.theheart.org, a Web site for cardiovascular healthcare professionals.
Heartwire from Medscape © 2008 Medscape
Cite this: Michael O'Riordan. Congress Sends Letters to ACC and AHA Over ENHANCE Press Release and Industry Funding - Medscape - Jan 25, 2008.