Merck should have included risk findings from the VIGOR study when promoting Vioxx to physicians before the data was added to labeling, FDA Office of New Drugs Director John Jenkins told a congressional hearing May 5.

"You do need to provide balanced information, and it would be important to provide information about the VIGOR trial once that became available," he said at a House Government Reform Committee hearing entitled "Risk and Responsibility: The Roles of FDA & Pharmaceutical Companies in Ensuring the Safety of Approved Drugs Like Vioxx."

Findings from the VIGOR study, which was designed to demonstrate the gastrointestinal profile of Vioxx (rofecoxib) compared to naproxen, showed an increase in cardiovascular risk for patients on the COX-2 inhibitor.

The study results were publicly available in March 2000, and therefore "physicians could have been aware, should have been aware of that data," Jenkins maintained.

However, Merck documents provided to the committee demonstrate that the company omitted VIGOR information from promotional materials during the period between the study's publication and its addition to labeling in 2002. Merck and FDA were in labeling negotiations regarding CV risks and gastrointestinal benefit for roughly two years.

In the interim, sales reps were directed to refer doctors with questions about VIGOR and the CV risk signals to Merck's medical services department. Reps also were repeatedly told to utilize a "cardiovascular card" distributed roughly a month after VIGOR results were announced to deal with physician concerns.

With over 20,000 internal documents provided by Merck to committee investigators, the majority of attention during the hearing focused on the "non-leave" CV card.

The tri-fold pamphlet included analysis of data culled from pre-approval trials on overall mortality and CV mortality for Vioxx compared to non-steroidal anti-inflammatories; the materials did not mention more robust data released from the post-approval VIGOR study.

Jenkins rebuked Merck for not including VIGOR data in detailing after it became available. "I don't know that I'd support the idea of not making it a part of the company's presentations to physicians," he said.

FDA Center for Drug Evaluation & Review Acting Director Steven Galson, who testified with Jenkins at the hearing, was less critical of Merck.

The company did not violate regulatory requirements by omitting risk information from detailing when the data was available but not yet found in labeling, Galson maintained. "In this particular case, when the label discussions weren't completed, the company wasn't required to put the information on."

Merck's CV card "was accurate based on the label, which is the legal standard we use," he declared.

Galson declined to pass judgment on Merck when asked whether the company's treatment of VIGOR results prior to 2002 fell short of ethical standards. "We think it's very important that the companies convey truthful information that is up to date with the scientific data that is available at the time," he responded.

Merck VP-Global Strategic Regulatory Development Dennis Erb repeatedly told the committee that sales reps did not discuss VIGOR prior to 2002 because the information was not included in approved labeling, in accordance with company policy.

Merck's prohibition regarding discussion of VIGOR came under fire during the hearing. Government Reform Committee Ranking Member Henry Waxman (D-Calif.), for instance, maintained that FDA regulations barring reps from talking about data on unapproved uses cannot be interpreted to forbid discussion of safety issues, even if the data are not included on labeling.

Waxman asserted that the data sales reps did refer to - from the CV card - were scientifically inappropriate, especially when far more valid information was available from VIGOR.

"These studies were not appropriate for an overall analysis of cardiovascular safety," Waxman said in a memo summarizing the committee's months-long investigation of Merck's promotional practices.

"One FDA medical reviewer, in a briefing this week with committee staff, said that the relevance of Vioxx's pre-approval studies to the drug's cardiovascular safety was 'nonexistent' and that it would be 'ridiculous' and 'scientifically inappropriate' to present mortality comparisons from these trials to physicians," the memo states.

Galson and Jenkins said that they had not seen the CV card prior to the day of the hearing.

Waxman also criticized Merck for continuing to forbid sales reps from discussing VIGOR even after the FDA Arthritis Drug Advisory Committee voted that doctors should be informed of its findings. Moreover, the sales force was told not to initiate discussion of the panel's meeting, he noted.

A script provided to sales reps the day after the advisory committee's vote provided specific guidance on responding to physician concerns (see chart: " ¹ Sticking To The Script ").

The company documents show that Merck reiterated its policy for sales reps - to cite the CV cards and refer specific questions to the medical services department - following subsequent press reports regarding Vioxx risks, including a study published in the Journal of the American Medical Association.

Rep. Gil Gutknecht (R-Minn.) said that if companies are unwilling to discuss safety data before its inclusion in approved labeling, lawmakers should consider allowing FDA to dictate labeling without negotiating with manufacturers.

Galson, however, indicated throughout the hearing that legislative action is not necessary to address the issues raised by Vioxx. Instead, he touted plans for the Drug Safety Oversight Board and drug safety website (see ² Also see "Drug Watch Website Data Is Not For Use In Advertising, FDA Cautions" - Pink Sheet, 9 May, 2005.).

No specific legislative plans were described by members, though Government Reform Committee Chairman Tom Davis (R-Va.) said the panel's investigation showed "the relationship between the Office of New Drugs and Office of Drug Safety has its challenges."

Davis did not mention the drug safety bill recently introduced in the Senate by Finance Committee Chairman Charles Grassley (R-Iowa) and Sen. Christopher Dodd (D-Conn.); the measure would establish a separate drug safety center.

However, committee members did discuss their investigative agenda, agreeing on plans to investigate Pfizer's promotional practices for its COX-2 inhibitors Celebrex and Bextra .

Rep. Elijah Cummings (D-Md.) was the first committee member to call for expanding its inquiry to include Pfizer "in fairness to Merck."

Waxman agreed that companies other than Merck should be scrutinized, though he did not refer to Pfizer by name. "We ought to get the documents from the other companies," Waxman said. "Whether we hold a hearing or not, that's something we can address later."

Committee Chairman Tom Davis (R-Va.) offered a qualified endorsement of the proposal. "We can do that. We obviously have priorities right now, but we can get the documents to look at," he said.

The unnamed drug manufacturers may not be viewed with as high regard as Merck, Waxman suggested. "It would helpful to get the documents, especially from those companies that we don't think of in the same high caliber as we think of Merck," he said.

[Editor's note: This story was contributed by " ³ The Pink Sheet ," your weekly source for prescription pharmaceutical news. For more information call 1-800-332-2181.]

Merck Vioxx Detailing Should Have Addressed VIGOR Risks – FDA’s Jenkins

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