Assault on Drug Marketing Tactics Becomes Drug Specific On Capitol Hill

This article is reprinted from "The Pink Sheet" - January 28, 2008

Pharmaceutical firms avoided a moratorium on direct-to-consumer television ads in the FDA Amendments Act, but that victory seems of little comfort now as Congress undertakes a wide-ranging probe of industry marketing practices.

A flurry of letters from House Energy and Commerce Committee leaders last week continued to question the motives of Merck and Schering-Plough in delaying the release of data from the ENHANCE trial for Vytorin.

The ENHANCE study, which failed to demonstrate that Vytorin (ezetimibe/simvastatin) is significantly better than simvastatin alone in preventing the formation of arterial plaque, was completed in April 2006. The results were unveiled Jan. 14, 2008.

The companies have temporarily pulled television ads for Vytorin and Zetia (ezetimibe), but questions remain, Energy and Commerce Oversight Subcommittee Chair Bart Stupak, D-Mich., said Jan. 23.

"Did they escalate their marketing efforts because they knew the drug did not work?" the congressman asked.

The companies strongly objected "to mischaracterizations about the ENHANCE" study delays. The trial remained blinded until Dec. 31, when Schering-Plough Research Institute statisticians began to access the data, the firms said in a Jan. 25 statement.

They also released labeling and other information, insisting that Vytorin and Zetia are effective in battling LDL cholesterol.

Drug Costs Prompt Push for Marketing Curbs

One reason for congressional concerns about advertising and other industry efforts to disseminate drug information is the high cost of drugs, WilmerHale partner Scott Lassman explained at a Washington Legal Foundation media briefing on Jan. 24.

"There is a widely held view that if you could cut down on marketing, you would drive down cost and utilization," he explained.

Cost appears to be at least one factor in the House panel's investigation. To obtain a view on the cost to consumers of delaying the ENHANCE results, Stupak and committee chairman John Dingell, D-Mich., have asked CMS Acting Administrator Kerry Weems to submit information on federal expenditures for Vytorin since the ENHANCE 2006 completion date.

"We are seriously concerned that while the manufacturers may have known that Vytorin was ineffective, huge sums of taxpayer dollars may have been spent on this expensive drug," they said in a Jan. 22 letter to Weems.

They also seek a briefing "on whether CMS has considered withdrawing payment for Vytorin based on its apparent lack of increased efficacy when compared to Zocor (simvastatin) alone, as well as how CMS makes decisions regarding payment for prescription medications that may be subsequently found to have little efficacy."

Financial Relationship to AHA, ACC Questioned

The ENHANCE trial also is giving the congressmen the opportunity to delve into the issue of drug companies' financial relationship with physician groups and organizations that provide public education on health issues.

Following the release of ENHANCE, the American College of Cardiology, the American Heart Association and the National Lipid Association urged caution in interpreting the results and said that on-going longer-term studies will be more informative about treatment options for reducing heart attacks or death.

But Dingell and Stupak note that Merck has invested millions of dollars in an ACC fellowship program and that Merck and Schering-Plough sponsor an AHA web site on cholesterol. AHA's web site "includes a page titled, 'The Two Sources of Cholesterol,' which seems identical to Merck/Schering-Plough's advertising campaign for Vytorin," they note in a Jan. 24 letter to AHA CEO Cass Wheeler.

Financial records from ACC and AHA are being sought so the oversight panel can "examine exactly how much funding these two organizations receive from Merck and Schering-Plough, how they use this funding and any potential conflicts of interest."

Sen. Chuck Grassley, R-Iowa, also has been probing the issue, and touted ACC's Jan. 25 "clarification" of its advice on ezetimibe. ACC noted that the drug is not approved for first-line use and that "the benefits of statins have been proven in large studies, while the effect of ezetimibe is unproven."

Stupak and Dingell also have asked Merck and Schering-Plough for information about stock sales by corporate officers, in light of significant sales by Schering-Plough Executive VP and President for Global Pharmaceuticals Carrie Smith Cox.

"We are complying fully with the [committee's] requests and we are providing information on a rolling basis," Schering-Plough told "The Pink Sheet."

Merck and Schering-Plough downplayed the financial impact of the ENHANCE study during recent talks with the investment community.

Controversy's Toll on Sales

But while dropping the TV ads, Merck and Schering-Plough have launched a print ad campaign in national and selected daily newspapers to stress Vytorin's LDL-lowering capabilities.

ENHANCE data showed that Vytorin lowered LDL levels by 58 percent after 24 months, compared to a 41 percent LDL decrease in the simvastatin group. Ads in consumer magazines and professional publications will continue in their previous form.

Prescription market share for Vytorin and Zetia dropped after the ENHANCE data were revealed, but have now flattened out, according to a Jan. 23 research note from Credit Suisse analyst Catherine Arnold. She said Vytorin's share of the cholesterol-lowering drug market was 11.1 percent and Zetia's 8 percent prior to the Jan. 14 data release.

Subsequently, Vytorin's low was 9.2 percent on Jan. 17. Zetia's share fell to a low of 6.5 percent on Jan. 18. "The prescription shares for both Vytorin and Zetia remain in the same range as they have been since they initially dropped," Arnold noted Jan. 25. Her analysis is based on IMS Health data.

FDA is reviewing the ENHANCE data, but any label change is many months off, and that will likely create another news event the firms will have to manage.

FDA Asked About Lipitor Ad

Congress's focus on pharmaceutical marketing is not limited to Vytorin alone. The Energy and Commerce Committee expanded its investigation into celebrity drug endorsements with a Jan. 22 letter to FDA Commissioner Andrew von Eschenbach. The panel's focus is on Pfizer's ad for Lipitor with artificial heart inventor Robert Jarvik.

The question put to FDA is whether the "Division of Drug Marketing, Advertising and Communications (DDMAC) has been involved with these Lipitor advertisements."

Dingell and Stupak are seeking "any records relating to the review or monitoring of said advertisements, complaints received relating to these advertisements, and any comments or consultations that DDMAC has provided relating to these advertisements."

Second-guessing of DDMAC DTC reviews could further undermine industry efforts to improve members' advertising image by getting agency input prior to publicly airing the ads.

Annual user fees of $6.5 million for DTC TV ad review have been eliminated from FDA's budget for fiscal 2008 and replaced with a $4 million appropriation. As a result, DDMAC will be reviewing ads "in as timely a manner as resources permit," instead of on the 45-day timetable anticipated under the user fees.

If DDMAC has to look over its shoulder for congressional oversight of individual ad reviews, review times are likely to be lengthened further.

Pharmaceutical Research and Manufacturers of America has codes of behavior with regard to DTC ads and marketing to physicians designed to improve members' marketing practices and forestall criticism.

Anecdotal reports indicate the codes have improved marketing behavior, Lassman told WLF. But "there are no good metrics" to show the codes' effectiveness since PhRMA does not monitor compliance nor enforce them, he said.

Industry financial dealings with physicians themselves are the subject of the Physician Payments Sunshine Act, S. 2029, which was introduced by Sens. Herb Kohl., D-Wis., and Grassley to create a registry of drug company payments and gifts to doctors.

- Cathy Dombrowski

Comments

[Ajlouny]

The FDA has a tough line to walk to try and get medications to people that can receive benefit, but not so early as to miss major problems. When side effects occur only in 0.1% of the subjects, you need to have 10s of thousands of subjects to really see it become statistically significant from placebo. Yes, it is sad that this happens, but there is just no way to prove that drugs are conclusively safe before they are approved.