Allergan, the drug company that makes and markets Botox®, has pleaded guilty to federal charges that it illegally marketed the drug for “off label”, or unapproved, uses. The company has agreed to pay $600 million to settle civil and criminal allegations.

Botox is most famous for being used by celebrities to reduce the facial wrinkles that naturally occur from age, mostly around the eyes, forehead and mouth. That version is called Botox Cosmetic, and its use was not in question.

Botox Therapeutic, however, at the time of the allegations, was approved for use for cervical dystonia, a chronic neurological movement disorder in which the neck turns involuntarily to the left, right, upwards, and/or downwards, sometimes seen as a tremor or repetitive shaking of the head. The Justice Department says Allergan promoted Botox for headache, pain, spasticity and juvenile cerebral palsy, exploiting its on-label cervical dystonia indication to build off-label pain and headache sales.

The Justice Department alleged that in 2005, Allergan paid doctors $1,500 to attend events promoting these off-label uses of the drug. Legally, doctors are allowed to use a drug for an unapproved use, but it is illegal for a drug company to market or promote such “off-label” uses.

The investigation was aided by Albert Hallivis, an Allergan employee turned whistleblower, who revealed to federal investigators that the company was urging doctors to prescribe Botox off-label. Hallivis, who remained an employee, said he became troubled when asked to violate federal law by marketing Botox for off-label uses. Hallivis called FDA's Help Line, filed a whistleblower lawsuit under the False Claims Act, and assisted Justice and the FBI in the investigation.

To accept the settlement, Justice said Allergan must drop its lawsuit filed in 2009 against the Food and Drug Administration, in which Allergan argued that its First Amendment rights allowed the company to educate doctors about using Botox safely, including off-label uses.

Many similar cases have arisen over the years, some more spectacular than others. Among the most spectacular was the record-breaking 2009 $2.3 billion settlement made against Pfizer Inc., the world's largest research-based pharmaceutical company (see Singer Health Report Vol. 13 Issue 32). Pfizer was cited for promoting off-label uses of its painkiller Bextra®. The Pfizer salesman who filed a “whistleblower” suit, a West Point graduate and Gulf War veteran, said that in the Army he was expected to protect people at all costs, but at Pfizer he was expected to increase profits at all costs — even when that meant endangering lives. Bextra was suspected of causing heart attack, stroke and pulmonary embolism (blood clot in the lung) and was removed from the market in 2005.

In the past, the FDA's primary response to issues regarding providing off-label information to doctors has been to first encourage the drug company to do the clinical testing needed for approval for that use, especially when it’s become a standard treatment by doctors. Pfizer’s position was that the expense of clinical trials is prohibitive when a drug is near the end of its exclusivity (patent protection). The company will never be able to recoup the high costs of clinical testing because the drug will become “generic” and will be made and sold more cheaply by other drug companies.

An interesting wrinkle (no pun intended) is that since the settlement, the FDA has approved several previously off-label uses for Botox Therapeutic, including some for which Allergan was charged. Nevertheless, a Justice Department official was quoted as saying that the government will continue to “aggressively pursue” all pharmaceutical companies that market drugs for off-label uses.

SOURCES: Joseph, Greenwald and Laake, P.A., September 3, 2010, http://www.prweb.com/releases/2010/09/prweb4455274.htm http://www.prweekus.com/justice-department-to-pursue-off-label-pharma-marketing/article/178144/