Recently in Marketing Category

In an ongoing effort to protect consumers from fraudulent cancer treatments, the FDA sent warning letters to 25 web-based businesses from April 17 to June 9. The warned companies or entities and a list of their 125 "fake cancer 'cure' products" were posted yesterday at the FDA web site. These letters follow a series of warning letters sent by the FTC earlier this year to 112 web sites, which falsely promoted cancer treatments, says the FDA. Consumer complaints and a web search performed by the FDA, FTC, and members of the Mexico-US-Canada Health Fraud Working Group prompted the overdue crackdown.

At least 3 of the targeted entities are already known to the FDA. A search of warning letters at Casewatch indicates that Vitasalus Inc (Nu-Gen Nutrition), Vitapurity, and H&L Worldwide all received earlier letters from the FDA, which claimed that the businesses promoted products for the "cure, mitigation, treatment, or prevention of diseases" in violation of the Federal Food, Drug, and Cosmetic Act. These repeat warnings do not necessarily include the numerous instances in which companies have fraudulently hawked the same products—for example, "Coral Calcium" or "Curcumin"—in rotating fashion as disease treatments.

An FDA warning letter sent to Vitasalus (Nu-Gen Nutrition) in May 2002 cited a single website, cancerchoices.com, and the product Squalamax. However, the most recent FDA letter cites 7 websites and 6 other products, in addition to Squalamax. A Wayback search reveals that 6 of the 7 Vitasalus websites named this year existed in 2002. The 2 other companies, H&L Worldwide (Chang Li) and Vitapurity (Otto Roder), have evidently not moved their cyber or land-based addresses since the time of their FDA warning letters in 2004 and 2005, respectively. Given the number of products promoted by each company and those cited by the FDA this year, business does not seem to have suffered for either company in the interim.

Leaders of the Energy and Commerce committee, John Dingell (D-MI) and Bart Stupak (D-MI), requested that 4 drug companies adhere to rules for direct-to-consumer (DTC) ads that are mostly already in place. The letters were sent May 20 to leaders at JNJ, Pfizer, Merck, and Schering-Plough following a May 8 congressional hearing, "Direct-to-Consumer Advertising: Marketing, Education, or Deception?" Responses to the representatives' letters were posted yesterday at the committee's website.

Today's media coverage largely focuses on the representatives' request for a voluntary, 2-year moratorium on DTC advertising of new drug products, which was declined by the companies. However, Dingell and Stupak made other requests, as described in sequence here:

1. That the companies follow the AMA's guidelines for the use of actors and health professionals in DTC ads.

The AMA's policy H-105.988 states that "product-specific DTC advertisements should not use an actor to portray a health care professional...because this portrayal may be misleading and deceptive. If actors portray health care professionals in DTC advertisements, a disclaimer should be prominently displayed." Also "[t]he use of actual health care professionals, either practicing or retired, in DTC to endorse a specific drug or implantable medical device product is discouraged but if utilized, the advertisement must include a clearly visible disclaimer that the health care professional is compensated for endorsement."

The representatives' request is, no doubt, a response to Pfizer's semi-controversial use of artificial-heart inventor Robert Jarvik to promote Lipitor in its now-pulled DTC ads. Pfizer replied to the committee that it is "currently working internally to ensure that the recent AMA guidelines...are fully incorporated into our DTC advertising when applicable." Merck responded that none of its current DTC ads use physicians or actors who play physicians. All companies, including JNJ and Schering-Plough, agreed to comply with the AMA policy in cases where it might be relevant.

2. That DTC ads not market products until a "valid outcomes study" is completed, and the results are released.

The representatives' definition of valid outcomes is not entirely clear; although they may be referring to longer-term clinical outcomes—for example, cardiac events instead of surrogate cholesterol levels in the case of cholesterol-lowering medications (ie, statins). Certainly DTC ads can only promote the use of FDA-approved pharmaceuticals, which must show at least clinically meaningful efficacy and safety to be approved. JNJ wrote that it has concerns about categorically prohibiting DTC ads "before completion of studies of an undetermined time and nature." Merck indicated that it would defer to the FDA on this point. Pfizer and Schering-Plough (which market Lipitor and Vytorin, respectively) indicated that waiting for long-term clinical outcomes would compromise consumer education and, therefore, consumer health.

3. As recommended by the Institute of Medicine, that there be a 2-year (instead of the conventional 6-month) moratorium on DTC ads for new prescription drug products.

In 2006, the IOM recommended that the FDA require a special product label to identify a new drug or new drug combination, and that DTC advertising should be restricted during 2 years. The FDA has not implemented the IOM's recommendation. All companies contacted by the representatives indicated that they abide by a general, internal 6-month moratorium on DTC advertising and would continue to do so. The companies cite PhRMA guidelines, which state that "companies should spend an appropriate amount of time to educate health professionals...before commencing the first DTC advertising campaign...[C]ompanies should take into account the relative importance of informing patients of the availability of a new medicine, the complexity of the risk-benefit profile of that new medicine and health care professionals' knowledge of the condition being treated."

4. That DTC drug ads should not market off-label uses.

Probably the most blatant example of grandstanding by the congressmen. Of course, DTC advertising must comply with FDA-approved labeling, and all companies indicated their compliance.

5. That DTC ads include the FDA's toll-free MedWatch phone number for reporting adverse events.

Current law mandates the listing of the MedWatch number in DTC print ads, and a toll-free information number in televised ads. JNJ indicated that it would include the MedWatch number in its TV ads. The other companies stated that they would defer to the FDA, pending the agency's ongoing investigation of this particular matter.

6. That so-called black-box warnings be included in DTC ads.

Merck and Schering-Plough indicated that they did not have any DTC ads for products with black-box warnings, and all companies replied that they have deferred (ie, Pfizer) or would defer to the FDA about how to incorporate such safety information into DTC ads.

HT for story: Pharmalot. 

In an expected move, representatives of the primary voting blocks of the AMA House of Delegates—primary care doctors, state medical societies, and specialty medical societies—strongly objected to an AMA proposal to eliminate commercially supported CME, according to today's Medical Marketing & Media. The AMA's Council on Ethical and Judicial Affairs (CEJA) had recommended the phasing out of nearly all commercial support for CME, an issue which was debated at a committee hearing on Sunday, during the annual meeting of the AMA House of Delegates in Chicago.

John Kamp, executive director of the Coalition for Healthcare Communication, reported that the proposal "went down in flames," according to the paper. The CHC, along with the North American Association of Medical Education and Communication Companies (NAAMECC), objected to the CEJA proposal on the basis of 3 general arguments:

[T]he report ignores the dramatic difference between certified CME and other non-certified 'education' and thus overlooks the significant advances in the management and resolution of conflicts of interest mandated in the last several years by government, industry and the [ACCME].

[T]he report's conclusions are not based on current and scientifically relevant and rigorous evidence in the context of certified CME and do not respect dramatic progress in the past decade.

[T]he report lacks a plausible, detailed plan to ensure that the proposed elimination of $1 billion in certified CME funding would improve the quality of certified CME and patient care.

Given the objections voiced at the AMA meeting, the CEJA proposal is "referred back to the council, effectively tabling it for the year," wrote the paper.

What's harder to get than a drug prescription from your doctor? Answer: an implanted stent from your doctor.

Nevertheless, there's much ado about a DTC television ad for the Cypher stent from Cordis (a JNJ subsidiary), which aired nationally last fall but can now only be viewed in the Baltimore area, according to the WSJ Health Blog. Today both the NYT and the WSJ report on an NEJM editorial against the ad, which was published online yesterday.

In the NEJM perspective, cardiologists William Boden, MD, and George Diamond, MD, question the propriety of airing a medical-device ad to "millions of people who are ill-equipped to make judgments about the many clinically relevant but subtle and complex therapeutic issues that even specialists continue to debate." Despite acknowledged benefits of DTC advertising to both the public and industry, the authors write that they are troubled by the limits of TV ads generally to disclose risks and find the Cypher ad, in particular, overpromising with respect to depicted functional outcomes.*

The curious aspect of the editorial, however, is Boden's and Diamond's objection to promoting a medical device that "can be selected and implanted only by someone with a very sophisticated medical understanding." They write, "It seems almost unimaginable that a patient would challenge an interventional cardiologist's judgment about the use of a particular stent or that a cardiologist would accede to a patient's request for a particular stent on the basis of the information gleaned from a television ad."

So at this point, I'm not sure what their objection is to the Cypher ad: Is the Cypher ad objectionable because it is misleading and therefore potentially harmful, or is the ad objectionable because it is useless, even absurd?

*Last year, Boden et al published "Optimal medical therapy with or without PCI for stable coronary disease," in which the rates of a number of vascular outcomes were no different between patients who underwent percutaneous coronary intervention and those who received optimal medical therapy alone. For what it's worth, Boden reports consulting fees from CV Therapeutics and PDL BioPharma; lecture fees from CV Therapeutics, sanofi-aventis, BMS, and Abbott; and grant support from Abbott.

Photo of Cypher (sirolimus-eluting coronary stent) from http://www.cypherusa.com/cypher-j2ee/cypherjsp/main_splash/stent.jsp.

Moving through the Web at warp speed.

As Jason Linkins at the Huffington Post indicates, we're probably familiar with the antidepressant's tagline only because we're taking the drug given the state of things.

Mike Huckman at Pharma's Market recently highlighted Pfizer's new, sober-looking DTC print campaign for Lipitor (atorvastatin), which may be taking advantage of Schering-Plough's recent woes with Vytorin (ezetimibe/simvastatin) and the exhaustively covered* ENHANCE study.

The print ad reads, "Unlike Vytorin and Zetia, Lipitor is FDA approved to reduce the risk of heart attack, stroke, and certain kinds of heart surgery in patients with several common risk factors for heart disease."

The head-slapping irony here is that Lipitor, when first FDA approved in 1996, was indicated to reduce LDL cholesterol but had not been shown to prevent clinical vascular events like its 4 existing competitors at the time. Nevertheless, Lipitor quickly became the number-one statin (and an uber-blockbuster) because 1) it reduced LDL cholesterol by a relatively greater percentage than the other statins and 2) clinicians believe (or at least believed) that the LDL cholesterol level is directly related to the risk of vascular events. Lipitor wasn't approved to reduce the risk of vascular events until 2004.

*But not entirely accurately covered.

Yesterday, the DoJ indicted W. Scott Harkonen, MD, former CEO of InterMune, for wire fraud and the misleading promotion of Actimmune (interferon γ-1b) for idiopathic pulmonary fibrosis (IPF). At the center of the case appears to be whether Actimmune, which was and is not FDA approved for IPF, was promoted by Harkonen for the treatment of the fatal condition on the basis of insufficient data. If convicted, Harkonen could face up to 20 years in prison.

 

In a press release yesterday, Harkonen's defense counsel* claimed that Actimmune "was supported by persuasive science as a new potential treatment for [IPF]," and that "the government is trying to criminalize an important potentially life-saving scientific debate." Harkonen was CEO of InterMune from February 1998 through June 30, 2003, and a member of the company's board of directors from February 1998 through September 2003. He is currently president and CEO of CoMentis, a small biotech operation in San Francisco.

 

According to the indictment, Harkonen directed the promotion of Actimmune for IPF and established sales goals toward that purpose in 2000, after a small, open-label trial of the drug indicated improved lung function in patients with glucocorticoid-refractory disease. The trial results were published in the NEJM in October 1999.

 

It is also alleged that Harkonen then fostered the company's public misrepresentation of results from a 2002 placebo-controlled, phase 3 trial of Actimmune in medically refractory IPF, GIPF-001. The trial results, according to the indictment, were negative; however, Harkonen then allegedly directed a post-hoc subgroup analysis of the trial data, which produced a statistical trend toward improved survival with Actimmune in patients with mild-moderate disease.

 

The indictment goes on to allege that Harkonen was instrumental in crafting the following press release, which was filed with the SEC, to promote the manipulated results of GIPF-001. (The Pathophilia blog has not been able to find a peer-reviewed report of the trial's results. Update: The GIPF-001 trial results were published in the NEJM in 2004 [Raghu G et al]. Actimmune, when compared with corticosteroids, did not significantly improve progression-free survival [the primary endpoint], pulmonary function, or quality of life.) 

 

INTERMUNE ANNOUNCES PHASE III DATA DEMONSTRATING SURVIVAL BENEFIT OF ACTIMMUNE IN IPF

—Reduces Mortality by 70% in Patients with Mild to Moderate Disease—

 

BRISBANE, Calif., August 28, 2002—InterMune, Inc. (Nasdaq: ITMN) announced today that preliminary data from its Phase III clinical trial of Actimmune® (Interferon gamma-1b) injection for the treatment of idiopathic pulmonary fibrosis (IPF), a debilitating and usually fatal disease for which there are no effective treatment options, demonstrate a significant survival benefit in patients with mild to moderate disease randomly assigned to Actimmune versus control treatment (p = 0.004). These data confirm the survival benefit seen in the Phase II trial presented earlier this year at the 98^th Annual Conference of the American Thoracic Society. There was also approximately a 10% relative reduction in the rate of progression-free survival associated with Actimmune versus placebo, the trial's primary endpoint, but this was not a statistically significant difference.

 

"We are extremely pleased with these results, which indicate Actimmune may extend the lives of patients suffering from this debilitating disease," said W. Scott Harkonen, MD, President and CEO of InterMune. "Actimmune is the only available treatment demonstrated to have clinical benefit in IPF, with improved survival data in two controlled clinical trials. We believe these results will support use of Actimmune and lead to peak sales in the range of $400-$500 million per year, enabling us to achieve profitability in 2004 as planned."

 

"The mortality benefit is very compelling and represents a major breakthrough in this difficult disease," said Ganesh Raghu, MD, Professor of Medicine, University of Washington in Seattle, and the Phase III study's lead principal investigator. "Interferon gamma-1b is the first treatment ever to show any meaningful clinical impact in this disease in rigorous clinical trials, and these results would indicate that Actimmune should be used early in the course of this disease in order to realize the most favorable long-term survival benefit."

 

The indictment further alleges that an e-mail containing instructions for presenting the GIPF-001 trial results was distributed to the InterMune sales force, and that InterMune hired a marketing research firm to determine whether the GIPF-001 press release would affect the prescribing habits of pulmonologists (the results: it would). The indictment also charges that Harkonen acted to disseminate "false and misleading" information through letters delivered to patients with their Actimmune medication and through letters that were fax-blasted to doctors, both of which were distributed by a Florida specialty pharmacy.

 

It is especially noteworthy that another phase 3 study of Actimmune, the INSPIRE trial, which began enrolling patients with mild-moderate IPF in December 2003, was terminated for lack of efficacy in March 2007. From 2000 to 2003, Actimmune sales were 90%-100% of InterMune's total sales, according to the indictment, and the "vast majority" of Actimmune sales were for IPF treatment, claims the DoJ. The estimated costs of 1 year's supply of Actimmune for one patient is $50,000.

 

A press release provided yesterday by InterMune establishes considerable distance between the company and its former leader. In October 2006, InterMune entered into a deferred prosecution agreement and will pay nearly $37 million "to resolve criminal charges and civil liability in connection with the illegal promotion and marketing of its drug Actimmune," reports the DoJ. InterMune is also evidently a party to a 5-year Corporate Integrity Agreement with the OIG.

 

A couple of more interesting quotes on the Harkonen indictment by government authorities, specifically with respect to individual culpability in the pharma industry and effects on government agencies, like the VA:

 

"Pharmaceutical executives who promote drugs using false and misleading information should not be allowed to hide behind a corporate shield," said Kim Rice, Special Agent in Charge of FDA's Office of Criminal Investigations, Washington Field Office. "Pharmaceutical companies do not run themselves, and those who engage in criminal conduct will be held personally accountable."

 

"The results of this criminal investigation show our commitment to protect the Veteran Administration’s healthcare system from deceptive and fraudulent practices by pharmaceutical companies," said Special Agent in Charge Douglas J. Carver of the US Department of Veterans Affairs, OIG.

 

*James J. Brosnahan. Check out the California firm's interesting domain name: "mofo."

 

Note: Yellow highlighting has been added by the Pathophilia blog.

 

Photo: www.7x7sf.com

Recognizing the undeniable marketing power of anecdotes, Jaan Siderov, MD, over at the Disease Management Care Blog* (DMCB) provides a handy promotional template for disease-management companies who find it easier to say, we don't have to show you any stinkin' evidence-based medicine.

*Looks like the DMCB and the Pathophilia blog are both December babies and will achieve their major motor milestones this year at approximately the same time. Pathophilia is currently working on its social smile.