Washington Editor

WASHINGTON – When it comes to violations of the Federal Food, Drug and Cosmetic Act (FDCA), it's usually the FDA going after a drugmaker. But Par Pharmaceutical Inc. has turned the tables on the agency, saying the FDA is violating the FDCA and the First Amendment by restricting truthful speech about approved uses of Par's Megace ES.

In a suit filed recently in federal district court, Par challenged FDA regulations that criminalize truthful speech about approved drug uses to physicians who may use the drug both on- and off-label. If Par succeeds with its lawsuit, the FDA's aggressive enforcement of "intended use" and off-label regulations could come to a screeching halt.

The agency bases its off-label enforcement on the fact that a drug's label doesn't include adequate directions for use for the off-label purposes.

But "when a manufacturer speaks about an on-label use of its drug in a medical facility where physicians prescribe the drug off-label," the suit said, "the manufacturer is caught in a Catch-22: changing the drug's labeling to add directions for the off-label use violates the [FDCA's] criminal 'new drug' rule, but based on the government's view of the FDA's 'intended use' regulations, not changing the labeling to add those directions violates the act's criminal misbranding rule.

"The manufacturer's truthful speech about on-label use of its drug thus violates at least one of these criminal provisions."

The lawsuit also questioned the legality of the FDA's broad definition of labeling. "By regulation, the FDA has dramatically expanded the scope of materials that constitute 'labeling'" by extending the narrow FDCA definition to cover any tangible material distributed by a drugmaker that contains information about a drug, Par claimed.

The company asked the U.S. District Court for the District of Columbia for a declaratory judgment, as well as preliminary and permanent injunctions to "ensure its ability to engage in this protected speech free from the risk of criminal liability."

The Woodcliff Lake, N.J.-based company was subpoenaed by the Department of Justice in 2009 and is under investigation for its marketing of Megace ES (megestrol acetate oral suspension), an appetite-stimulating hormone approved in 2005 to treat anorexia, cachexia and AIDS-related wasting.

Even before Megace ES was approved, other formulations of megestrol acetate were commonly used, off label, to treat wasting in geriatric and cancer patients, Par said in the lawsuit. Today, the majority of Megace prescriptions are off label. In fact, when the FDA approved Megace ES, the agency acknowledged that the hormone would be used for off-label indications. And Medicaid and Medicare continue to reimburse for the off-label use of the drug. (See BioWorld Today, Oct. 14, 2008.)

Par has tried to conduct the placebo-controlled trials necessary to support labeling for wasting in cancer patients. But megestrol acetate has become the de facto standard of care for the indication, so such trials are ethically impossible, the drugmaker said.

At this point, Par said it's afraid to talk to physicians in long-term facilities or cancer practices about the approved uses of Megace even though these doctors treat AIDS patients who could benefit from the therapy.

In its investigation into the company's past marketing practices, the government has told Par that a drugmaker that wants to discuss approved uses in a setting where physicians use a drug both on- and off-label "must first confirm that there are presently a sufficient number of patients being treated for whom the drug could be prescribed on-label," according to the lawsuit.

But the government has provided no guidance on what constitutes a "sufficient number" of patients, Par said.

As a result, the FDA's actions have chilled Par's truthful speech, the drugmaker said, adding that the agency's regulations are arbitrary, capricious, an abuse of discretion and contrary to constitutional rights.

Pfizer Pays $14.5M to Settle Final Off-Label Case

New York-based Pfizer Inc. agreed last week to pay $14.5 million to settle False Claims Act charges related to the off-label marketing of Detrol (tolterodine), which is approved to treat overactive bladder.

According to whistleblower claims, Pfizer promoted the drug for use in men suffering from benign prostatic hypertrophy and several related conditions, such as lower urinary tract symptoms and bladder outlet obstruction. The whistleblowers will receive more than $3 million from the settlement, with the rest of it going to the federal government and state Medicaid programs, according to a Department of Justice press release.

The settlement resolves the last of 10 whistleblower suits filed against Pfizer, beginning in 2003. The other nine suits were settled or dismissed two years ago as part of a $2.3 billion settlement. (See BioWorld Today, Oct. 14, 2008.)

Bill Aims at Spurring Antibiotic Development

A bill to spur development of new antibiotics was introduced in the Senate last week with bipartisan support. The Generating Antibiotic Incentives Now Act, which mirrors a bill introduced in the House in June, is aimed at combating the spread of antibiotic-resistant bacteria. The legislation would provide incentives for R&D for innovative antibiotics and fast-track FDA review.