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Apr-13-2008The Vytorin Letters(topic overview)
CONTENTS:
- In a letter Friday, Rep. John Dingell (D., Mich.), chairman of the House Energy and Commerce Committee, and Rep. Bart Stupak (D., Mich.), chairman of the Subcommittee for Oversight, asked why minutes of the companies' ad hoc expert panel, which met in mid-November, were "created after the fact" in December. (More...)
- Delay aided sales Vytorin sales boomed during the delay in the release of research showing the drug had failed to improve artery health. (More...)
- The dispute over the minutes involves a meeting of imaging experts the companies convened for advice on how to deal with the imaging issues. (More...)
- The results were formally presented at a major cardiology conference last month. (More...)
- Vytorin, which was developed and marketed jointly by Merck and Schering-Plough, was approved for use by the Food and Drug Administration in 2004. (More...)
- The e-mail was forwarded to Enrico Veltri, the Schering-Plough executive helping run the trial. (More...)
SOURCES
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In a letter Friday, Rep. John Dingell (D., Mich.), chairman of the House Energy and Commerce Committee, and Rep. Bart Stupak (D., Mich.), chairman of the Subcommittee for Oversight, asked why minutes of the companies' ad hoc expert panel, which met in mid-November, were "created after the fact" in December. The release of the documents is the latest development in a controversy about Vytorin and sister drug Zetia that has swept Merck and Schering-Plough into a firestorm over the drugs' value in fighting heart disease and over drug-industry behavior in the conduct of clinical trials intended to prove the safety and benefits of their products. [1] WASHINGTON, April 11 (Reuters) - Two top Democrats investigating why Schering-Plough Corp (SGP.N: Quote, Profile, Research ) and Merck & Co's (MRK.N: Quote, Profile, Research ) delayed the release of data on their cholesterol drug Vytorin said their probe has uncovered "some unusual circumstances" and is far from over, according to a letter released on Friday. U.S. House of Representatives Energy and Commerce Committee Chairman John Dingell and Rep. Bart Stupak, chairman of the oversight and investigations subcommittee, said they "continue to have serious concerns regarding the conduct and reporting" of the drugmakers' controversial trial, called Enhance.[2]
Rep. John D. Dingell (D-MI), Chairman of the Committee on Energy and Commerce, and Rep. Bart Stupak (D-MI), Chairman of the Oversight and Investigations Subcommittee, today wrote to the CEOs of Schering-Plough Corporation and Merck & Co, Inc., requesting additional information about the ENHANCE study trial. This latest information request follows a review of documents related to conduct and reporting of the study. '''We continue to have serious concerns about the handling of the ENHANCE trial and the release of its results,''' said Dingell.[3]
Rep. John D. Dingell (D-Mich.), chairman of the House Committee on Energy and Commerce, and Rep. Bart Stupak (D-Mich.), chairman of the Oversight and Investigations Subcommittee, who are conducting an investigation of the companies' handling of the ENHANCE data, released 70 pages of documents that, taken together, paint a picture of the ENHANCE sponsors seeking a back door out of a negative finding.[4]
House of Representatives Energy and Commerce Committee Chairman John Dingell and Rep. Bart Stupak said company documents showed minutes from a November meeting of outside experts reviewing the study were "created after the fact." The documents showed one of the experts complained the minutes did not reflect all the opinions expressed, although he said a later summary did. A company spokeswoman said participants in the meeting had been told no minutes would be produced, so none were -- until the Food and Drug Administration later requested them.[5] The five-member panel of medical advisers were told that no minutes or transcript of the meeting would be taken, the lawmakers note. Committee Chairman John Dingell and Subcommittee for Oversight Chairman Bart Stupak began investigating in December how Merck and Schering-Plough handled data comparing Merck's Zocor against their new cholesterol drug Vytorin.[6] Merck & Co. and Schering-Plough Corp. created minutes of a crucial meeting about a major study on their cholesterol drug Vytorin after a congressional panel began an investigation, drawing objections from one participant that the document didn't accurately reflect the meeting's conclusions, according to documents obtained by a congressional subcommittee. • The News: A House committee said documents obtained from Merck and Schering-Plough indicate the companies created minutes of a meeting involving their Vytorin study a month after the event. • Why It Matters: The minutes may have been drafted after Congress began an investigation of the Vytorin study, which raised doubts about the drug's effectiveness. • Researcher Comments: One of the outside researchers says that no minutes were taken at the meeting and that they aren't accurate on a key point.[1] Learn how to maintain seamless business continuity while migrating from traditional voice mail, to unified communications. The latest in joint congressional investigations is based on e-mails between a University of Wisconsin-Madison cardiologist and officials with the drug companies Merck and Schering-Plough, which are the midst of an ongoing controversy over whether they deliberately delayed the release of research results showing that the drug did not improve artery health. Two members of a congressional committee investigating the matter asked the chief executives of both companies why minutes of the expert panel meeting in November were "created after the fact," especially after members of the expert panel were told there would be no minutes or transcript of the meeting.[7]
Combined sales of the drugs were $5.1 billion last year. The companies have denied any such strategy and have said the delay resulted from their efforts to resolve problems in imaging data gathered for the study. A Schering-Plough spokeswoman acknowledged that no minutes were kept at the Nov. 16 meeting but said notes were taken, and the minutes eventually were produced, because the Food and Drug Administration requested them. She said that the panel agreed with the final version of the minutes and that it was "unanimous in their opinion that it would be reasonable for the study team" to change the primary endpoint. The companies said the documents released by Rep. Dingell "are entirely consistent with the account of the facts" as the companies have disclosed them publicly.[1] The documents dredged up by congressional investigators show friction developing between Merck and Schering-Plough so intense that it led one executive to swear and new questions about why the results were not released sooner. As previously reported by Forbes, they show minutes were created for a key meeting after the fact. At least one panel member argued with the companies over the content of this document. While it previously appeared the companies had pulled TV ads for Vytorin mainly because of the study, Dingell and Stupak, both Michigan Democrats, released a letter warning Merck and Schering they would have to make new, prominent claims about Vytorin's lack of efficacy over a cheaper generic drug, Zocor.[8]
"Our investigation has uncovered some unusual circumstances which has raised new questions for Merck and Schering-Plough about why the companies waited so long to release the study results," said Dingell, in a statement. Merck and Schering have previously said they did not delay releasing the results to boost sales. Schering said it would cut $1 billion in annual costs by 2012 and slash 10 percent of its staff amid wide expectations that sales of Vytorin and Zetia will soon plunge. Merck and Schering once heavily advertised Vytorin and Schering-Plough's Zetia, which brought their joint venture $5.1 billion in 2007 sales. Their stocks have dipped to 12-year lows, and they've been hit with numerous lawsuits.[6]
Crestor is AstraZeneca's third best-selling drug, with sales of $2.8 billion in 2007. At the same time Merck and Schering-Plough were dealing with the bad news on their drugs, AstraZeneca was delivering good news on Crestor. The company announced March 31 that it was stopping its 15,000-patient "Jupiter" clinical study after Crestor showed "unequivocal" evidence of lower death rates in patients with normal cholesterol levels but high levels of C-reactive protein (CRP), which is linked to heart problems. In a conference call, University of Chicago cardiologist Michael Davidson said the Jupiter study, whose results have yet to be presented in their entirety, should expand the number of patients who will be treated with the cholesterol-lowering drugs known as statins.[9]
Based on a survey of doctors, analysts from Deutsche Bank forecast "abrupt and sustained declines" in usage of Vytorin and Zetia, cholesterol drugs marketed jointly by Merck & Co. and Schering-Plough Corp. The report follows the release of a study on the drugs at a cardiologists' meeting in late March and a recommendation from an expert panel that the drugs be used only as a last resort.[9] April 11 (Bloomberg) -- Merck & Co. and Schering- Plough Corp. may have fabricated the account of an expert panel's meeting on a controversial study of the cholesterol drug Vytorin, a member of that group said.[10]
WASHINGTON (Reuters) - Two U.S. Democrats said on Friday their investigation had raised questions about how Merck & Co Inc (MRK.N: Quote, Profile, Research ) and Schering-Plough Corp (SGP.N: Quote, Profile, Research ) documented a key meeting about a controversial study of their Vytorin cholesterol drug.[5]
Democratic leaders of the House Energy and Commerce Committee have sent a letter drug makers Merck and Schering-Plough, which makes a similar medicine, Zetia. They want to know why minutes from a meeting about the cholesterol drug last November were written after the fact. One meeting participant objected to the minutes, saying they distorted the account of panel's discussion and recommendation.[11] Democratic leaders of the House Energy and Commerce Committee sent a letter to the companies Friday asking why minutes from a November meeting about the blockbuster cholesterol drug were created after the fact, in December.[6]
Democratic Representatives John Dingell and Bart Stupak of Michigan, members of the House Energy and Commerce Committee, are probing whether the companies intentionally sought to alter or delay results from the Enhance study. The lawmakers released e-mail records today from Schering- Plough showing Stein opposed the company's effort to submit an account of the meeting that he said misrepresented what went on.[10] "I thought I was brought in as an expert scientist to give my honest opinion on the data." Stein said he did not see proof of "anything nefarious," but added, "it's possible that I'm just nave." In one of his e-mails, Stein objected to a statement that the panel had unanimously agreed to change the main objective of the clinical trial. "This really overstates our recommendation," Stein said. "We did not vote on this. It was a decision by the company to change the endpoint." In a Jan. 3 e-mail, Stein concludes by telling the company, "I cannot 'OK' or 'approve' this document," referring to a draft of the minutes. In a statement, Merck/Schering-Plough said it was cooperating with the House Energy and Commerce Committee in its investigation.[7] The panel of heart doctors convened in November by Merck and Schering-Plough didn't recommend altering the main endpoint of the drug trial as the companies claimed, Stein said in a phone interview. The companies' statement that they intended to change the study's goal prompted a congressional committee to question whether the drugmakers were trying to suppress negative data.[10]
"All panel members agreed that the final minutes were accurate, and the suggestion that the final endpoint be changed was not presented by Merck, Schering-Plough but was proposed by the panel itself,'' said Merck spokeswoman Mary Elizabeth Blake, in an e-mailed statement today. The companies announced in November that they would change the Enhance study's design after it was completed.[10]
On Nov. 19, Forbes reported on concerns about the delays in the ENHANCE study (see "The Vytorin Question" ). That night, Merck and Schering-Plough issued a press release saying that an anonymous expert panel had advised them to take the extremely irregular step of changing the study's main goal, as set forth before the trial began.[8] Shares of Merck and Schering-Plough, which sell Vytorin through a joint venture, have fallen sharply since the results of the study, named Enhance, were released in January. Dingell and Stupak, both Michigan Democrats, said they "continue to have serious concerns regarding the conduct and reporting" of the Enhance trial.[5] In January, Merck and Schering-Plough issued a long-delayed report on the results of the ENHANCE trial which tracked the buildup of fatty plaques in patients using Zetia-plus-Zocor combo Vytorin, compared to patients using Zocor (simvastatin) alone.[12]
Expect AstraZeneca's Crestor to emerge as the big winner in the aftermath of Merck/Schering Plough's Vytorin debacle, primary care physicians (PCPs) said. Results of a new survey conducted by Deutsche Bank (DB) and ImpactRx indicate Vytorin and Zetia prescriptions written by PCPs will continue their decline as the number of Crestor scripts rises. In a note to investors this week, DB pharmaceuticals analyst Barbara Ryan presented the results of the survey of 101 PCPs, examining their prescribing habits for cholesterol drugs and anticipated changes in the wake of the presentation of results of the ENHANCE trial at last month's meeting of the American College of Cardiology (ACC). '''Together these data points suggest both additional abrupt and sustained declines for Vytorin and Zetia and increased utilization of other statins, especially Crestor,''' Ryan wrote. Survey results indicated that Vytorin share on average will decline from its current 16% share to 9% and Zetia share will dip from 9.5% to 6%.[12] The decreased usage reflects not only fewer new patient starts but also a large increase in switching off to other agents from about 16% to 38% in the future. '''Despite a modest recent recovery in new prescription levels for Vytorin and Zetia following the initial January decline, the ENHANCE trial news at ACC appears to have had an immediate negative impact on prescribing practices of both PCPs and cardiologists,''' Ryan concluded. According to the survey, use of other statins will also increase; however, the primary beneficiary in terms of share gains appears to be Crestor, both from future anticipated use by PCPs and immediate changes seen in prescribing, especially by specialists.[12]
WASHINGTON, April 11 -- Documents released here today indicated that Merck and Schering-Plough seriously considered changing the endpoints of the ENHANCE trial on ezetimibe/simvastatin (Vytorin) and, failing that, to cover up the attempt.[4] The inner workings of the companies revealed in the documents from Dingell and Stupak, stand in stark contrast to the glowing account of "standard operating procedure for Schering-Plough trials" described yesterday by the ENHANCE trial's sole U.S. investigator, Evan A. Stein, M.D., Ph.D., of the Metabolic and Atherosclerosis Research Center in Cincinnati. In an exclusive MedPage Today interview, Dr. Stein said the delays, while annoying, were due to the meticulous care and strict adherence to protocol that Schering-Plough demands in all its trials.[4]
The letter was among 70 pages of documents on the panel meeting released today by Dingell, who is chairman of the energy committee, and Stupak, who heads the investigations subcommittee. Stein said the "overall tone of the minutes makes it seem as if the conclusions represented strong, unanimous, scientific recommendations of the panel, when they really were opinions with varying degrees of enthusiasm from individual panel members, varying degrees of scientific justification and varying degrees of consensus.''[10] Merck said in a statement Friday that Stein and the other panelists later agreed that a final version of the minutes was accurate. Panelists also agreed that they proposed the idea to change the Vytorin study goal, Merck said. In their letter, Dingell and Stupak ask Merck and Schering chief executives to provide additional details about the meeting and the marketing for Vytorin.[6] Stein takes issue with the companies' statement that panelists unanimously recommended changing a key goal of the Vytorin study to highlight more favorable results. "This really overstates our recommendation," Stein wrote. "It was the decision of the company to change the endpoint." Merck and Schering ultimately decided against changing the study goal, although company scientists gave permission for such a change in late November. Stein concludes his Jan. 3 e-mail by telling Merck he will not approve their version of the meeting.[6]
Lawmaker angered In a statement, Grassley said Merck/Schering-Plough delayed publication of the Vytorin trial "for marketing purposes." "When a company bills the federal government hundreds of millions of dollars for a single drug, then it's important for the government to know how the drug works and that the therapy is cost-effective," he said. Grassley sent a letter last month to Merck and Schering-Plough executives saying he was troubled by reports that the companies delayed the results of the Vytorin trial. "Since the (Vytorin) trial was completed in 2006, the federal government has paid M/SP (Merck/Schering-Plough) hundreds of millions of dollars for Vytorin," he said.[7] One has to raised about why many companies wait long to release the study results. Merck has a history of hiding the truth about it's drug trials.[3]
Lawmakers have been investigating the circumstances around a failed study of the drug. It showed that Vytorin was no better at limiting plaque buildup in arteries than an older drug, Zocor, now available as a generic. The study was completed in 2006, but the companies didn't release those results until January after Congress began investigating the delayed study.[11]
U.S. Reps. John Dingell and Bart Stupak on Friday released new documents they say raise "serious concerns" about the delay of reporting key results of a key study of the cholesterol-lowering drug Vytorin.[8] The nearly two-year delay in the release of the research was unusual and raises "serious concerns," Reps. John Dingell and Bart Stupak said in their letter to the chief executives of Merck and Schering-Plough.[7]
Delay aided sales Vytorin sales boomed during the delay in the release of research showing the drug had failed to improve artery health. Asked whether his panel may have been used by the company to further delay the research, Stein said, "I just don't know. [7] Prescriptions for Vytorin and Zetia had already been on the decline since mid- January, when ENHANCE was first released.'' It was thought prescription volume would recover, but those hopes have mainly been dashed since the calls for reduced usage made at the medical meeting March 30. Already, Schering-Plough - where sales of Vytorin and its sister drug Zetia accounted for 60% of profits - is bracing for the hit its bottom line will sustain from the debacle.''[13] WASHINGTON (AP) — House Democrats are questioning whether Merck and Schering-Plough made up information about a meeting of medical experts to discuss Vytorin, after lawmakers began investigating a failed study of the drug.[6] CAPITOL HILL (AP) -- House Democrats are questioning whether two drug companies made up information about a meeting of medical experts to discuss Vytorin.[11]
The dispute over the minutes involves a meeting of imaging experts the companies convened for advice on how to deal with the imaging issues. After he received a copy of minutes to approve, Dr. Stein wrote in an email to a top scientist at Schering-Plough: "It was my understanding that there were no minutes or transcript of this meeting." About the companies' description of the panel's advice on changing the primary endpoint, Dr. Stein wrote: "The tone here implies that we strongly recommended this when in reality we just advised you on what the scientifically valid approaches would be." [1] Stein and four other experts were hired as part of an independent advisory panel by the companies. In e-mails that Stein gave to the committee, he states that there were no minutes or transcripts of the meeting. He also said that some of the statements that were made in the re-created minutes did not fit his recollections of the meeting and that they were inaccurate in the portrayal of opinions of the panel members.[7]
"The study remained blinded until shortly before that date.'' Stein said participants in the November meeting of scientific advisers were told no minutes would be taken so they could freely express their opinions. Draft versions of the minutes submitted to the panelists later didn't accurately reflect what had occurred, he said. "Since there was no audio or written transcription of the meeting, I still have a hard time calling this document `minutes,''' Stein said in a letter to Schering-Plough asking him to approve the document.[10] A document, labeled as minutes and submitted to lawmakers investigating the handling of the study, was created a month after the meeting and didn't accurately reflect the viewpoints of the panel, University of Wisconsin cardiology professor James H. Stein, who was one of the participants, said today.[10]
The "minutes" suggest that the company wanted to change the trial's endpoint to images of the common carotid artery, rather than the endpoint stated in the study protocol, which was intima-media thickness measured at the right and left common carotid, carotid bulb, and internal carotid. The "minutes" stated that the expert panel recommended this change. Dr. James Stein objected, writing, "This was not a conclusion of the meeting." He shared his objections with Congressional investigators, resulting in a mother lode of notes, emails, and drafts that provided a glimpse into the mood of the sponsors in the months before the data were finally made public.[4] Merck/Schering-Plough did not record the daylong meeting with the three imaging experts -- J. Robin Crouse, M.D. of Wake Forest University; James Stein, M.D., of the University of Wisconsin; and Michiel Bots, M.D., Ph.D., of the University of Utrecht in Holland -- and statistician Greg Evans, M.S., of Wake Forest; and David Orloff, M.D., a regulatory expert from a clinical trials company, Med Pace, in Cincinnati. The companies wrote "minutes" about a month later and sent them to participants for approval. That, it turned out, was a misstep because Dr. James Stein objected to many of the statements in the document, including the characterization of the document as "minutes."[4]
In documents released by the committee, one of the consultants took issue with that statement in the minutes. James Stein, a cardiac-imaging expert at the University of Wisconsin, told a company scientist in an email: "We did not vote on this.[1]
One panelist, James Stein, a cardiac imaging expert at the University of Wisconsin, disagreed with assertions made in the document. "This really overstates our recommendation," Stein wrote to Schering-Plough executive John Strony. "It was the decision of the company to change the primary endpoint."[8] The centerpiece of that meeting with three experts in Doppler imaging of intima-media thickness, a statistician, and a regulatory expert, was a company proposal to change the study's primary endpoint.[4]
"In particular, the draft and final minutes of the expert panel meeting on November 16, 2007, make clear that there were significant scientific and technical questions presented by the analysis of the data.," Merck/Schering-Plough said. "Efforts to deal with those questions, and to ensure the accuracy of the final results, were the reason the study results were not released until January 2008."[7] Included in the documents from Dingell and Stupak was an agenda for a Nov. 16 meeting of an expert panel called to advise the companies about "scientific" ways to handle the data.[4] Now, Dingell and Stupak's investigation puts the focus squarely on an expert panel that met on Nov. 16, 2007, to address apparent problems with the ENHANCE data.[8]
The Nov. 16, 2007, meeting's minutes were circulated among the participants on Dec. 19, a week after an investigation by a panel of the House Energy and Commerce Committee began.[1]
Dingell is chairman of the committee on energy and commerce and Stupak is chairman of the subcommittee on oversight and investigations. The congressmen cited e-mails their committee obtained from James Stein, a UW-Madison cardiologist.[7] Dingell and Stupak, chairman of the oversight and investigations subcommittee, are probing why the companies did not release the study findings until 20 months after it ended.[5] '''Our investigation has uncovered some unusual circumstances which has raised new questions for Merck and Schering-Plough about why the companies waited so long to release the study results.'''[3] The documents were made public along with a letter sent to the drug's makers, Merck (nyse: MRK - news - people ) and Schering-Plough (nyse: SGP - news - people ). The congressmen say they are continuing their investigation.[8]
The document was created based on notes from the discussion after the Food and Drug Administration requested minutes of the meeting, according to Merck.[10] E-mails released by the Michigan Democrats Friday show James Stein, a University of Wisconsin professor, objected to Merck's recollection of the Nov. 16 meeting. "I still have a hard time calling this document 'minutes'," wrote Stein, in an e-mail to company executives. "They at best are an incomplete summary of what transpired at the meeting."[6]
On Sept. 14, 2007 Soren Christiansen, a Merck employee, sent an email to "the board," expressing concern about treatment of John Kastelein, M.D., of the Academic Medical Center in Amsterdam in Holland, ENHANCE's principal investigator, by the companies. "During a meeting at Dr. Kastelein's Hospital it was agreed to conduct a meeting with outside consultants by mid-September," he wrote and then forwarded an email from Dr. Kastelein complaining that no meeting had taken place.[4] New prescriptions for Vytorin were down last week, following last month's recommendations from some top cardiologists that Vytorin be used only as a last resort.'' That recommendation followed the release of the ENHANCE study that showed Vytorin worked no better than cheaper cholesterol medications.[13] The disputed study, called Enhance, showed Vytorin worked no better at unclogging arteries than Zocor, which is available in generic form for a fifth of the cost.[10]
Last month, published clinical trial results showed that while the combined drug, Vytorin, reduced cholesterol about 17% more than just Zocor, there was no significant difference in the plaque thickness found in the carotid arteries of the 720 patients in the trial.[7] Results of the ENHANCE trial suggested that while the combination drug does a better job of lowering LDL (bad cholesterol), Zetia did nothing to enhance the atherosclerosis-slowing benefits of Zocor, which lost patent protection in mid-2006.[12]
The drug did not show a benefit on the vascular wall despite an impressive 56% reduction in LDL, which was 16% better than the reduction achieved by simvastatin alone in ENHANCE. The trial tested the strategy in patients with familial hypercholesterolemia.[4]
The ENHANCE study was run by Schering-Plough under an arrangement in which Merck and Schering divvied up key clinical trials.[8] Results of the ENHANCE study, completed in April 2006, were to be released by March 2007, but the companies stalled, citing data complexity.[12] The ENHANCE study, which was released on January 14, showed that Vytorin and Zetia were ineffective in preventing clogged arteries, and might actually increase plaque in some users.[13]
The study failed to prove that Vytorin, a combo pill of Zocor and the drug Zetia, did any better at preventing heart-attack-causing atherosclerosis than older medicines.[8] Heavy marketing Vytorin combines the drugs ezetimibe (Zetia) and simvastatin (Zocor), two drugs that work in different ways to lower cholesterol.[7] According to the report issued Tuesday, Crestor has already seen a bump in prescriptions since the cardiologists' meeting and will be the primary beneficiary of the decline in Vytorin and Zetia usage. A survey conducted for Deutsche Bank found that Vytorin and Zetia could lose more than 10 percent market share, while Crestor is in line to up its share more than 4 percent, which would give it nearly one-fifth of the cholesterol drug market.[9]
The analysis in the New England Journal of Medicine said that Zetia and Vytorin sales were displacing traditional statin drugs, which have proven benefits in reducing heart attacks and strokes.[7] For the first three quarters of 2005, Merck/Schering-Plough spent $115 million on DTC ads for the drug, according to TNS Media Intelligence figures, and the joint venture spent another $94 million on consumer ads for the same period in 2006. Consumer advertising for the brand is handled by DDB New York, while professional advertising for both Vytorin and Zetia is handled by Corbett Accel.[12]
More than $200 million was spent on direct-to-consumer advertising for Vytorin in the U.S. during 2007, resulting in sales that exceeded $5 billion, according to a special article published in the New England Journal of Medicine.[7] Vytorin, which had sales of $5 billion a year, accounts for the majority of Schering-Plough's profits.[5] Vytorin and Zetia, with $5.2 billion in sales last year, are Schering- Plough's most important products, accounting for about 70 percent of profit.[10]
Since it came on the market, Vytorin sales have reached $5 billion per year.[13]
The results were formally presented at a major cardiology conference last month. The delay led cardiologists and public officials such as Rep. Dingell to ask whether the companies had long known the trial had failed and had deliberately withheld the finding to protect surging sales. [1] The full airing of the trial results occurred March 30 in a presentation at the American College of Cardiology meeting and the results were simultaneously published in the New England Journal of Medicine.[4]
"We wish to note that the documents released by the Committee are entirely consistent with the account of the facts relating to the (clinical trial) that we have given to the public and to the Committee staff," the statement said.[7] Scientific challenges held up the analysis of the data, Schering-Plough spokeswoman Rosemarie Yancosek said today in an e-mailed statement. "Efforts to deal with those questions, and to ensure the accuracy of the final results, were the reason the study results were not released until January 2008,'' she said.[10] Merck and Schering-Plough said at the time that the decision was based on the expert panel's recommendation to speed an analysis of the data.[10] Merck and Schering-Plough share the revenue from Vytorin, a combination of Schering-Plough's Zetia and Merck's Zocor.[10] Besides, Schering-Plough still had some unfinished business: Years earlier, the company had set out to prove that Vytorin -- a combination of Zetia and Zocor -- worked better than Zocor alone.[14]
Vytorin, which was developed and marketed jointly by Merck and Schering-Plough, was approved for use by the Food and Drug Administration in 2004. [13] The documents include a letter from the division of the U.S. Food and Drug Administration that says the companies would have to include additional information about Vytorin's risks and benefits.[8]
Dingell and Stupak are pushing for a wider investigation of Vytorin's effectiveness and of the amount spent on the drugs by the federally funded Medicare and Medicaid plans.[1] Rick." Grassley, Dingell, and Stupak all say both Senate and House investigations are continuing, with demands for more answers from Merck/Schering-Plough as well as the FDA.[4]
In the fallout from the ENHANCE controversy, a massively successful advertising campaign for Vytorin was pulled off the airwaves. Public appearances might not have been the only reason for that decision, Dingell and Stupak allege in their letter.[8]
The study showed Vytorin was no better than a cheaper generic drug at reducing plaque in neck arteries.[5] New prescriptions for Vytorin fell by 35 percent after the study's release in January.[10]
A panel of four doctors concluded that Vytorin should be used only as a last resort, considering that the expensive drug did not provide any added benefits.''[13] According to Verispan, a drug data research firm, total U.S. Vytorin prescriptions for the week ended April 4 were flat with the week ended March 28, at about 306,000.''[13] Grassley said the e-mails indicated that Merck/Schering-Plough had devised an aggressive seven-week media blitz that was designed to get doctors to switch patients to Vytorin from cheaper statin drugs.[7] The FDA said the advertisements should convey, in consumer-friendly language, "that taking the combination drug Vytorin has not been shown to provide any additional cardiovascular outcome benefits compared to using Zocor alone."[8]
The minutes suggest that the outside consultants had recommended a critical change in the primary endpoint -- the main measure for how the drug would be evaluated.[1]
The e-mail was forwarded to Enrico Veltri, the Schering-Plough executive helping run the trial. [8] In spite of the findings, Merck and Schering-Plough delayed releasing ENHANCE for more than a year ''' something critics of the company have likened to fraud.[13]
SOURCES
1. Accuracy of Minutes On Vytorin Meeting Raises Doubt - WSJ.com
2. US lawmakers cite unusual finding from Vytorin probe | Markets | Markets News | Reuters
3. The Science Business by Matthew Herper
4. Medical News: Congressional Revelations Document Pre-Release Intrigues on ENHANCE - in Geriatrics, Coronary Artery Disease from MedPage Today
5. Lawmakers question makers on key Vytorin meeting | Reuters
6. The Associated Press: Dems Question Timing of Vytorin Papers
7. Vytorin minutes disputed: Firms wrote experts' meeting notes later
8. The Vytorin Letters - Forbes.com
9. AstraZeneca eyes market share | delawareonline | The News Journal
10. Bloomberg.com: Worldwide
11. KGAN :: CBS 2
12. Crestor to benefit as ENHANCE smoke clears: survey - Medical Marketing and Media
13. New Vytorin Orders Fall
14. The Science Business by Matthew Herper
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