Infergen Promotion Produced By Third Party Lands Kadmon In Hot Water With DDMAC

FDA's Division of Drug Marketing, Advertising and Communications cites Kadmon for failing to include risk information and overstating efficacy in a "STATgram" promoting its hepatitis C treatment interferon alfacon-1.

A third party-produced promotional piece that referred readers to a website for risk information on Infergen (interferon alfacon-1) and left out a crucial part of the indication for the hepatitis C treatment drew an FDA warning letter for Kadmon Pharmaceuticals.

Infergen is a Three Rivers Pharmaceuticals product, but the Division of Drug Marketing, Advertising and Communications warning letter is addressed to Samuel Waksal, the chairman and CEO of Kadmon, which bought Three Rivers last October (Also see "Back In Biotech, Waksal's Kadmon Emerges From Stealth Mode To Focus on Hep C" - Pink Sheet, 2 Nov, 2010.)).

The offending piece is a "STATgram," a trademarked "communication product" or direct mailer produced by life sciences PR firm Cegedim. On its website, Cegedim describes the STATgram as "a carrier of important pharmaceutical product safety information, particularly 'Dear Health Care Professional' letters required by the U.S. Food and Drug Administration when regulatory updates are determined for FDA-approved prescription drugs."

DDMAC's attention was drawn by a complaint filed as part of the "Bad Ad" program, which encourages physicians to report possibly violative drug promotions to the agency (Also see "FDA Deputizes Doctors In Hunt For "Bad Ads"" - Pink Sheet, 11 May, 2010.).

Infergen is indicated for chronic hepatitis C in patients age 18 and up with compensated liver disease. It is part of a portfolio of HCV products Kadmon put together by buying Three Rivers and signing strategic agreements with Valeant Pharmaceuticals.

Crucial Omissions

The STATgram claimed that "Infergen is now approved for daily dosing with ribavirin for retreatment of HCV patients," according to the warning letter - a claim that left out the crucial limitation to compensated liver disease patients and made it sound as if "Infergen plus ribavirin is approved for retreating all patients infected with the hepatitis C virus."

Moreover, the promotion should have said that the safety and efficacy of Infergen in combination with ribavirin have not been evaluated in treatment-naive patients or patients who are co-infected with hepatitis B virus or HIV-1, and also should have addressed various important efficacy limitations, such as patients who are less likely to benefit from retreatment with combination therapy, the warning letter said.

On the risk side, the STATgram briefly mentioned some risks and referred readers to the product website, leaving out a range of information on serious risks, including potentially fatal reactions, the risk of serious birth defects for pregnant women on combination HCV therapy, and other items included in boxed warnings on the label, the warning letter says.

The STATgram also stated two claims based on underpowered open-label studies, made an additional claim that appeared to be without any foundation, and failed to include adequate directions for use, the warning letter says. Claims based on inadequate clinical trial evidence are a frequent citation in DDMAC warning and notice of violation letters (Also see "Seeking To Broaden Market For Feraheme, AMAG Runs Afoul Of DDMAC" - Pink Sheet, 22 Mar, 2011.).

A Private Company

Waksal, the former CEO of ImClone Systems, served five years in federal prison on insider trading charges related to that company, so Kadmon has to remain a private entity while he is involved in it under the terms of his plea arrangement with the Securities and Exchange Commission. A Kadmon spokesman mentioned the company's private status in declining to discuss sales figures for Infergen.

"The issues referenced by FDA pertain to a STATgram mailing for Infergen which was developed and approved by Three Rivers Pharmaceuticals prior to its acquisition by Kadmon," the company said in an emailed statement. "We are in the process of reviewing all promotional materials to confirm compliance with applicable law, and are working with the agency to complete this process."

- Martin Berman-Gorvine ([email protected])