A Bitter Pill to Swallow – The Perils in Off Label Promotion

On September 29, the US. Attorney's Office for the Northern District of California announced that a former CEO of InterMune was convicted of wire fraud for the "creation and dissemination of false and misleading information about the efficacy of InterMune's drug Actimmune (Interferon gamma-1b)." 

There are several interesting insights from this case.  Here is what happened.  The label of Actimmune states that the drug is approved as a treatment for "reducing the frequency and severity of serious infections associated with Chronic Granulomatous Disease" and for delaying the time of disease progression in patients with severe, malignant osteopetrosis.  

The company had begun a clinical trial called INSPIRE which was exploring the use of Actimmune in the treatment of idiopathic pulmonary fibrosis ("IPF"), which is a fatal disease.   In 2007, after an interim analysis, it was announced that the INSPIRE trial would be halted because there was not a significant difference between the treatment arm and the placebo arm in patients in the clinical trial.  This was the second time the company conducted a trial for IPF that failed.  

The conviction of the former CEO was based on evidence at the trial that he had earlier caused InterMune to issue a "press release publicly announcing results of a clinical trial of Actimmune for the treatment if IPF" even though the clinical trial in that regard had failed.  According to the New York Times reporting on the conviction, the sales of Actimmune peaked in 2003 and the bulk of the sales were for the off-label use of the drug to treat IPF.  In 2002, the company had issued a press release stating "InterMune Announces Phase III Data Demonstrating Survival Benefit of Actimmune in IPF".  The subheading was "Reduces Mortality by 70% in Patients with Mild to Moderate Disease."

Again, according to the times, while the initial trial for the treatment of IPF failed, the company saw that if you looked at people with only mild or moderate disease, then there was a positive effect.  

In October 2006, the company entered into a deferred prosecution agreement and paid $37 million to resolve criminal charges and civil liability in connection with illegal promotion.  

A search for a warning letter from FDA to InterMune about off-label promotion could not be found.  

There are few takeaways from this story:

  • When dealing with a drug that is already on the market, but going for a new indication, don't make claims on data that is being re-cut or re-interpreted that the FDA where the FDA hasn't endorsed the point of view;
  • The absence of a Warning or Untitled letter from the FDA does not mean that the U.S. Attorney's office won't act; 
  • The settlement by a company on the matters does not shield its executives;
  • A single, simple press release based on self-interpreted data can cause a lot of damage.

Be careful out there.  

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3 Responses to A Bitter Pill to Swallow – The Perils in Off Label Promotion

  1. Arnold I. Friede says:

    In addition to Mark Senak’s thoughtful and informative post, readers of Eye on FDA may wish to consider two additional legal aspects of this criminal conviction that merit special attention.
    First, while the off-label promotion of Actimmune for an unapproved use in Idiopathic Pulmonary Fibrosis (IPF) was lurking in the background, the specific charges against Medimmune’s former CEO, Dr. Scott Harkonen, were not based on off-label promotion as such. Instead, the Government charged Dr. Harkonen with felony wire fraud and misbranding based on false or misleading representations about the attributes of Actimmune. This required the Government to prove that the statements in the Press Release misrepresented the results of the study of Actimmune in IPF and were disseminated with an intent to defraud. It was not enough for the Government to prove merely that Actimmune was not approved for IPF. It seems clear, based on the conviction for wire fraud, that the jury found that the claims in the Press Release were false or misleading and made with an intent to defraud.
    Second, absent more, mere “news” about the results of a clinical trial reported in a Press Release would ordinarily be regarded as “scientific speech” that FDA lacks authority to regulate as advertising and promotion. In fact, public companies often have a duty under the securities laws to report such clinical trial results if they could have a “material” impact—good or bad—on the company’s financial results. At the same time, the charge against Dr. Harkonen was that he orchestrated a campaign that went beyond issuance of “news” and involved, among other things, very direct and explicit instructions to the Field Sales Force to disseminate the Press Release to physicians and to use it as the basis for promotional claims. The lesson in this is probably that if it walks like a duck and talks like a duck, it probably IS a duck, even though it is called a Press Release. In other words, something is regulable by FDA as advertising and promotion (and possibly labeling) not because of what the company calls it (in this case, it was called a Press Release). The underlying question, that the jury resolved adversely to Dr. Harkonen, is what the company is doing with the information. Here, the Government alleged, and the jury concluded, that the so-called Press Release amounted to fraudulent advertising and promotion. This does not categorically condemn all Press Releases, but it does suggest that they be reviewed with some care and their dissemination carefully limited to traditional “news” channels.
    Arnie Friede
    Office: 212.585-0411 Cell: 917.514.9166
    Admitted In: CA, CT, DC, MD

  2. Mark Senak says:

    Excellent insight, as always, from Arnie.

  3. GreatFred05 says:

    But Harkonen was aquitted of mis-branding. It was only the press release that was in question. And the government said the press release was factually correct – they disagreed with the statistical conclusions derived from the results. Seems to me that that IS an assault upon scientific free speech.

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