Marketing: March 2008 Archives

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.