The Free Speech Pill
Drug Firms See Opening to Push for End to Off-Label Marketing Ban
By THOMAS M. BURTON
Drug makers are mounting a legal campaign to overturn longstanding U.S. regulations prohibiting them from pitching medicines for uses not listed on the bottle.
Doctors routinely prescribe such therapies as a hemophilia drug for brain hemorrhage, and cancer drugs for a wider array of tumors, in situations where federally approved medicines aren't believed as effective or simply don't exist.
A pair of legal developments could let drug makers pitch products to treat ailments not listed on the medicine bottle, a practice long outlawed by federal regulators. Thomas Burton has details on Lunch Break.
But drug companies can't market those uses thanks to decades-old restrictions from the Food and Drug Administration. Federal prosecutors have secured settlements totaling billions of dollars from companies including Pfizer Inc., AstraZeneca PLC and Eli Lilly & Co. for allegedly violating the rules.
Now, several court cases and legal filings are threatening to erode that set of rules. Within weeks, a federal appeals court in New York is expected to decide whether Alfred Caronia, a former salesman for the company now known as Jazz Pharmaceuticals Inc. of Palo Alto, Calif., violated the law when he sold the narcolepsy drug Xyrem to treat other forms of drowsiness and chronic fatigue. He was convicted in a lower court on a criminal charge.
But his case got a boost in June, when the U.S. Supreme Court cited the First Amendment in striking down a Vermont law that prohibited using pharmacy records in drug marketing. In its decision, the court wrote that speech used in drug marketing is a form of expression protected by the Free Speech Clause of the First Amendment. That opened the door for Mr. Caronia's attorneys to argue his off-label marketing was simply free speech.
These and related legal developments "may put the FDA's ban on off-label promotion in some jeopardy," says Richard Cooper, a former FDA chief counsel now with Williams & Connolly in Washington.
Wayne Pines, another former FDA official and a consultant to the drug industry, says "these cases raise fundamental questions about the way the FDA regulates marketing materials." Neither Mr. Cooper nor Mr. Pines is involved in these cases.
The drug industry has made the free-speech argument before, and there is no certainty the New York appellate court will get to the constitutional issues or that the case will go on to the Supreme Court. But the direction of the current Supreme Court—and its willingness to introduce the First Amendment in striking down such laws—could alter the regulatory landscape, lawyers say.
Big drug makers, emboldened by decisions of the high court, have jumped into the Caronia appeal. In a "friends of the court" brief [SEE ATTACHED PDF FILE], and in other legal actions around the U.S., the industry is challenging the FDA on the rules more forcefully than before.
In the brief, Pfizer, GlaxoSmithKline PLC, Johnson & Johnson and eight other companies wrote that "off-label use is a necessary and common practice," and that applying the FDA's off-label rules to Mr. Caronia's alleged conduct "appears to be constitutionally indefensible" given the Supreme Court ruling.
A group of seven big drug companies filed a July petition with the FDA contending that the rules' "lack of clarity places manufacturers at risk of criminal and civil sanctions if they cannot correctly guess where the government would draw a line."
Whatever happens in Mr. Caronia's case, it's too late for his co-defendant, Maryland psychiatrist Peter C. Gleason. He gave paid talks for Jazz and pleaded guilty to a federal off-label marketing charge. The Annapolis doctor hanged himself in February. His sister Sally Goodson, says her brother's suicide "was directly because of this case."
The Caronia case is squarely focused on off-label marketing, and his lawyers have raised the First Amendment defense. The federal appeals court judges in New York have asked for briefs on how the Supreme Court decision affects their case.
Last month, Par Pharmaceutical Inc. sued the FDA and Department of Justice in federal district court in Washington, arguing that free-speech principles bar the FDA's off-label rules. Par has said in a court filing it wants to market Megace, a drug approved to treat AIDS-related weight loss, at long-term care facilities that also house cancer and geriatric patients.
Thomas W. Abrams, director of the FDA's Division of Drug Marketing, Advertising and Communications, says the off-label rules are in place for safety reasons.
"FDA does not want pharmaceutical companies promoting something as safe and effective when that hasn't been proven," he says. "Think of someone you love the most. Would you want that person on a drug that's not proven simply because the drug was promoted in such a way?"
He cites the example of estrogen. It was sold for decades as beneficial to heart health, but more recent research shows a complex mix of danger and benefit, depending in part on the age of the woman using it. The FDA is concerned that heavy marketing for unproven uses will multiply the number of people exposed to danger.
Medtronic Inc.'s bone-growth protein Infuse has been widely used off-label by orthopedic surgeons, doctors say. But in 2008, the FDA warned that its off-label use in neck spine operations had led to life-threatening swelling in the neck and throat that caused difficulties swallowing and breathing. Medtronic says it included warnings about Infuse use in the neck prior to 2008 and said it is committed to further research on the product.
Many off-label uses haven't triggered safety concerns. Government reports and medical journal articles have estimated that half or more cancer patients receive off-label drugs because studies required for drug approval can take so long. Yet companies cannot market for these uses.
Companies have paid a high price over the last two decades for allegedly violating off-label marketing rules. Of 31 drug cases settled under the False Claims Act from 1996 through 2010, 15—totaling $8.7 billion—involved off-label or fraudulent marketing and the related charge of misbranding, according to a September article in Archives of Internal Medicine.
In the largest such case, Pfizer agreed in 2009 to plead guilty to a federal criminal charge of illegally marketing the painkiller Bextra off label and to pay $2.3 billion for illegally promoting it and other drugs.
Write to Thomas M. Burton at firstname.lastname@example.org
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