Amgen in December pleaded guilty to off-label promotion of its $2-billion anemia drug Aranesp (darbepoetin alpha) and was fined $150 million, as part of a broader $762-million settlement with the US government. The charge resolves a series of criminal and civil allegations of illegal marketing practices around several other drugs, including rheumatoid arthritis treatment Enbrel (etanercept). In what began as a whistleblower lawsuit by a former sales executive and evolved into a full-blown federal government investigation, the Thousand Oaks, California–based Amgen was accused of misbranding Aranesp in renal disease at higher, less frequent dosages than those approved by the US Food and Drug Administration (FDA), to gain market share from Johnson & Johnson's Procrit (epoetin alpha). Amgen was also charged with marketing Aranesp for unapproved use in chemotherapy-induced anemia, and with offering illegal kickbacks to doctors.

Credit: Associated Press

This was the latest in a string of drug firm settlements related to off-label promotion. Coming just days after a US appeals court decision to overturn sales rep Alfred Caronia's conviction for promoting off-label use of Dublin-based Jazz Pharmaceuticals' drug Xyrem (sodium oxybate) on the basis of his First Amendment right to free speech, the fine restoked the debate around what constitutes off-label promotion, and whether FDA rules in this regard are stifling commercial speech. As dissenting US Court of Appeals judge Debra Ann Livingston noted in court, “if drug manufacturers were allowed to promote FDA-approved drugs for non-approved uses, they would have little incentive to seek FDA approval for those uses.” To date, apart from Caronia, FDA has struggled to stay within the boundaries of the First Amendment and issue criminal prosecutions for off-label promotions, notes John Engel, founding partner at Engel & Novitt in Washington, DC. FDA is reviewing its guidelines, including those on how to deal with physicians' unsolicited requests for off-label information. But “given the dictates of the First Amendment, it's very challenging to put down in black and white what's allowed and what's not,” notes Engel. Chad Landmon, partner at Axinn, Veltrop Harkrider in Hartford, Connecticut, reckons the agency has already clamped down over the last few years and that any new guidelines “won't bring significant changes.”