Cephalon's Promotion of Actiq

The Wall Street Journal reported the latest story about allegations of company promotions of off-label use of their pharmaceutical products. The allegations were about Cephalon's promotion of Actiq, a formulation of the synthetic narcotic fentanyl provided in a sweet-tasting lollipop. The US Food and Drug Administration had approved the drug for the treatment of intractable pain in patients with cancer. According to the WSJ, (somewhat re-ordered)

From setting unrealistically high sales quotas to pushing larger prescriptions at higher doses, drug maker Cephalon Inc. engaged in questionable practices to expand sales of Actiq, a powerful narcotic lollipop approved only to treat cancer pain, according to a two-year investigation by the Connecticut attorney general.
Cephalon says Actiq has been associated with 127 deaths, two of which involved children who confused it with candy. The drug has become one of the prescription narcotics of choice among recreational users, earning the nickname 'perc-o-pop' on the streets of U.S. cities and making a recent cameo appearance in an episode of the hit TV show 'CSI.' In the first nine months of this year, Actiq sales reached $471 million.

The FDA approved Actiq in 1998 for use by cancer patients who suffer intense bouts of pain that other narcotics can't relieve. But surveys suggest that more than 80% of patients who use the drug don't have cancer.

The trigger for Mr. Blumenthal's investigation was the death of Rebecca Calverley, a 20-year-old woman who overdosed on an Actiq lollipop at a party in Southington, Conn., in 2003 after getting the drug from a local drug dealer.

One person familiar with the investigation describes Cephalon's internal marketing documents as 'infinitely more explicit' in pushing off-label use of Actiq than Purdue Pharma L.P. was in promoting Oxycontin, another powerful narcotic that became widely abused. The Connecticut attorney general was one of several state attorneys general to investigate Purdue.

Mr. Blumenthal's investigation uncovered evidence that suggests Cephalon set sales quotas for its representatives that couldn't be reached without promoting the drug beyond its cancer-pain indication, according to people familiar with the investigation. Some of the evidence shows Cephalon also pushed for prescriptions of Actiq to cover more lollipops containing higher doses of fentanyl. Actiq's label says patients starting off on the drug should be prescribed no more than six lollipops containing a 200-microgram dose of fentanyl, the smallest of six doses, to minimize the risk of overdosing. Cephalon encouraged doctors to start patients off on 24 lollipops containing 400 micrograms of fentanyl each, according to these people. The higher dose costs more and brings in more revenue.

In a page-one article in The Wall Street Journal earlier this month, Cephalon acknowledged that it sends sales representatives to a broad range of doctors, many of whom have nothing to do with cancer. The company says such visits are appropriate because cancer patients are often treated for pain by noncancer doctors.

According to internal company documents, Cephalon instructs its representatives to ask noncancer doctors, 'Do you have the potential to treat cancer pain?" Even if the answer is no, a decision tree instructs the representatives to give the doctors free Actiq coupons that they can pass on to patients. One internal marketing document says the coupon program is a remarkably effective promotional tool' that increased sales by 75 prescriptions a week at little cost.

Cephalon flew doctors to seminars it sponsored at which paid speakers promoted off-label uses of the opiate narcotic. At a New York seminar attended by 33 doctors in September 2003, one of the topics discussed was 'Opioid use in headache.' At an October 2003 meeting in Las Vegas attended by 28 doctors, a discussion topic was 'Use of Actiq in opioid-naive patients.' Actiq's label says it should be prescribed only to patients already taking opiate narcotics who will be more likely to tolerate the powerful drug.

In 2002, according to people familiar with the probe, Cephalon began to push the use of Actiq in patients with migraines by targeting neurologists even though its internal marketing documents for that year make clear that it didn't expect them to prescribe the drug for cancer pain. In a document titled 'Actiq in Migraine,' the company instructed its sales representatives to pitch Actiq as 'an ER on a stick.'

What is distressing in the series of stories about promotion of off-label use of drugs (e.g., see our most recent post on the promotion of Neurontin) is the participation of physicians as paid pitch-men, or women. It is true that physicians are free to advocate for any off-label use of drugs they favor. But how can a physician who is paid by a company to give a talk that promotes off-label use of that company's drug deny that he or she is acting like a paid marketer?

At the very least, physicians giving such talks should disclose that they have been paid by the manufacturer to promote their drug. If they find doing so embarassing, maybe they should re-consider why they are giving such talks in the first place. (I would further suggest that promoting narcotics for pay may be particularly embarassing.)

Obviously, physicians in the audience should be properly skeptical of all pharmaceutical, bio-technology, and device marketing, whether it is done by former cheer-leaders or medical doctors.