Cephalon Drug Is Tied to Several Deaths

By JOHN CARREYROU and JACOB GOLDSTEIN

Drug maker Cephalon Inc. sent letters to doctors this week warning them that several deaths have been linked to Fentora, its powerful narcotic to treat acute cancer pain.

Fentora and its predecessor, Actiq, are approved by the Food and Drug Administration only for use in cancer patients, but they are often prescribed by physicians "off-label" for such ailments as headaches and back pain.

Cephalon denies marketing the two drugs outside their indication, but its marketing practices are under scrutiny in three separate probes: investigations by the U.S. attorney in Philadelphia and the Connecticut attorney general, and a congressional probe into off-label treatments.

Fentora and Actiq contain fentanyl, a highly addictive substance 80 times as potent as morphine. Fentanyl is classified as a Schedule II substance by the Drug Enforcement Administration, which puts it in the same category as cocaine and methamphetamine. Schedule II drugs have the highest potential for abuse and an associated risk of fatal overdose.

Cephalon said Fentora has been linked to a total of four deaths. The company said three of those, which appeared to result from respiratory failure, were related to inappropriate prescribing of Fentora. Two of the patients were prescribed the potent drug for headaches even though they weren't on round-the-clock opiate therapy, the company said. The company said it also received a report of a fourth death, a person who committed suicide while taking the drug but wasn't prescribed the drug by a doctor.

Doctors are allowed to prescribe drugs as they see fit, including for off-label uses. But off-label marketing by drug companies is illegal.

"We have been monitoring this issue," said FDA spokeswoman Susan Cruzan. "The FDA takes this very seriously, and we are working with the company to assure the safest possible use of this medication." The agency didn't address who might be at fault in the deaths.

In 4 p.m. Nasdaq Stock Market composite trading, Cephalon shares fell $3.99, or 5.2%, to $72.55 on the news.

The company said 78,000 prescriptions were written for Fentora between its launch in October 2006 and September 2007. Fentora is a faster-acting and more discrete version of Actiq, which is a lozenge on a stick that looks like a lollipop. Actiq has been associated with more than 120 deaths, including two involving children who confused the drug for candy. Doctors attributed some of the deaths to patients' cancer. More than two-thirds of the deaths occurred during clinical trials before Actiq hit the market in 1999.

In a page-one article in November, The Wall Street Journal reported that an analysis of prescription data over a 17-month period showed more than 80% of the patients who used Actiq didn't have cancer.

A spokeswoman for Cephalon, Stacey Beckhardt, said she didn't know what the proportion of off-label use was for Fentora. But she added: "We do know that some of the physicians who were prescribing Actiq are prescribing Fentora in the same way."

Connecticut Attorney General Richard Blumenthal's investigation, which began in 2004 and is ongoing, has found that Cephalon promoted Actiq off-label to neurologists to treat headaches, set unrealistically high sales quotas for its drug representatives and pushed larger prescriptions at higher doses, according to people familiar with the probe.

"Today's report by Cephalon tragically confirms concerns raised by our aggressive investigation into Cephalon's off-label marketing of its drugs," the Connecticut attorney general's office said in a statement.

A person familiar with the matter said Cephalon is "in active discussions" about a possible settlement with the Connecticut attorney general and the U.S. attorney in Philadelphia, though the talks are at a sensitive stage and might break down. Any settlement would involve a large fine and require that Cephalon take remedial measures to reform its aggressive marketing practices, this person said.

Cephalon declined to comment on the various investigations but said they were ongoing and it continued to cooperate with each one. Cephalon's Ms. Beckhardt said the company "promotes its medications consistent with the labeled indication" and added that it was "taking active steps to re-emphasize the importance of adhering to the labeling information" for Fentora.

Write to John Carreyrou at john.carreyrou@wsj.com

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