Whither Off-Label Communications Policy?

Another federal court ruling asserts that manufacturers may provide truthful information on off-label uses of medicines, further challenging FDA’s long-held policies for regulating prescription drugs. FDA officials have been planning a “comprehensive review” of agency regulations and

Jill Wechsler

guidance documents related to first amendment protection of free speech since the landmark 2012 U.S. v. Caronia decision, acknowledging the need to harmonize “fundamental public health interests” with the “dissemination of truthful and non-misleading information.” That initiative apparently was on hold pending a decision in the Amarin Pharma v. FDA case, but now expectations for change are high.

Just how these legal decisions affect FDA’s broader program for testing and approving new biopharmaceuticals remains to be seen. While pharma companies and first amendment lawyers have been pressing for more flexibility in discussing off-label uses, such changes raise questions about how much clinical evidence FDA will require to approve added indications for a marketed therapy. There appears to be tension within the agency between those who support a more liberal communications approach, and those who fear that will encourage sponsors to parlay approval of a narrow indication into much broader use of a therapy for untested purposes. If sponsors look to cut post-approval research programs, FDA then may become more cautious about approving new drugs based on limited evidence, undermining efforts to speed important new therapies to market.  

It’s ironic that the Amarin decision coincided with the death of Francis O. Kelsey, who kept thalidomide off the market in the early 1960’s, preventing a major US public health crisis. That possibility, though, led to enactment of the 1962 amendments to the Food, Drug and Cosmetic Act, which authorized FDA to require clinical studies documenting a drug’s efficacy as well as safety, and that marketing a drug for unapproved uses constitutes misbranding. FDA told the court that the Amarin challenge made a “frontal assault” on its new drug approval process. But Judge Paul Engelmayer of the US District Court for the Southern District of New York rejected that argument, noting that the 1962 amendments predate several key cases protecting free speech under the first amendment, including the Supreme Court’s 2011 decision in Sorrell v. IMS Health as well as Caronia.

Unless FDA appeals the Amarin decision, which is not expected at this point, the Ireland-based firm may provide truthful information on the use of Vascepa (icosapent ethyl) in additional patient populations without the threat of criminal prosecution. Amarin made a strong case for doing so, which won’t apply to most therapies: it developed Vascepa under a special protocol assessment (SPA) with FDA; it is funding a large cardiovascular outcomes trial; planned communications are limited to health professionals; and marketers of dietary supplements containing omega-3 fatty acids are free to make similar claims. Amarin has to provide certain disclosures with off-label information and must track that its statements remain fair and truthful as new scientific knowledge emerges.

Push for change

At the same time, Judge Engelmayer clearly concluded that truthful and non-misleading speech alone is not evidence of criminal misbranding, ratcheting up pressure on FDA to revise multiple policies related to disseminating information on unapproved drug uses. The agency has said it will respond to a citizen petition filed with FDA by the Medical Information Working Group (MIWG) in 2011 and again in 2013 that seeks clarification of procedures for pharma companies to deal with unsolicited requests, engage in scientific exchange, interact with formulary committees and payers, and disseminate clinical practice guidelines. And Congress approved a provision in the 21st Century Cures legislation requiring FDA to issue draft guidance in 18 months on disseminating truthful scientific information involving off-label uses.

Last spring, FDA general counsel Elizabeth Dickinson said that FDA

would schedule a public meeting in the summer on regulatory policy and first amendment issues, but the agency has been slow to set a date. The Amarin ruling now “leaves little room for FDA to protect its existing enforcement scheme,” says attorney John Kamp of the  Coalition for Healthcare Communication. “Normally, the agency might go back and think about it, and gradually loosen restrictions,” notes Dan Mendelson, president of Avalere Health. Now pressure from the courts and Congress will “force FDA’s hand.”

Agency officials feel they have been responsive to the changing policy environment, issuing guidance in 2011 that outlines a process for manufacturers to respond to “independent requests” for information on off-label uses. Another advisory in 2014 discusses distribution to health professionals of scientific and medical publications involving unapproved uses. FDA also has sought to revise communications policy to reflect seminal changes in information technology that undermines manufacturer control over statements about their products on the Internet and through social media. Curbs on off-label communication in a world where anyone can broadcast medical opinions appear unfair and inappropriate, but recent FDA draft guidances on how companies should respond to social media postings seem to raise more questions than they resolve.

Until FDA clarifies these and other rules, no one expects any surge in pharma off-label communications, no surprise in the wake of billion-dollar penalties on firms accused of bringing false claims against the government by promoting unapproved uses. FDA’s chief counsel may scrutinize more closely enforcement letters citing companies for off-label promotion from FDA’s Office of Prescription Drug Promotion (OPDP). Such added review could reduce such citations, and maybe even curb cases brought by the HHS Inspector General and the Department of Justice that charge misbranding based on off-label marketing.

But the Amarin ruling doesn’t legalize off-label communications based on research or claims that FDA determines are incomplete or fraudulent, explains Alston & Bird attorney Marc Scheineson. “So if FDA alleges that something is false and misleading, it still will win.”

Jill Wechsler is Pharmaceutical Executive's Washington correspondent. She can be reached at jwechsler@advanstar.com