Healthy Skepticism Library item: 6405

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Publication type: news

Carreyrou J.
Narcotic 'Lollipop' Becomes Big Seller Despite FDA Curbs Actiq Is Only for Cancer Pain But Cephalon Pitches It To Many Types of Doctors 'Like the Most Delicious Candy'
Wall St Journal 2006 Nov 3
http://online.wsj.com/services/article/SB116252463810112292-search.html?KEYWORDS=Narcotic+%27lollipop%27&COLLECTION=wsjie/6month

Full text:

Narcotic ‘Lollipop’ Becomes
Big Seller Despite FDA Curbs Actiq Is Only for Cancer Pain But Cephalon Pitches It To Many Types of Doctors ‘Like the Most Delicious Candy’
By JOHN CARREYROU
November 3, 2006; Page A1

While pregnant with her second child three years ago, Tiare Frontera
suffered from bad migraines. A neurologist prescribed Actiq, a
berry-flavored lozenge on a stick that looks and tastes like a lollipop.
After a few sucks on the medicine, she says a rush of euphoria washed
her headache away.

Soon, Mrs. Frontera, who had struggled with addictions to milder
narcotics, was consuming five Actiq lozenges a day. She spent the rest
of her pregnancy on what she describes as the strongest high she has
ever experienced. When she gave birth, her baby son was cranky and
wouldn’t sleep. Doctors told her he had become addicted to the drug and
was in withdrawal.
[Tiare Frontera]

Mrs. Frontera is one of thousands of Americans who are prescribed Actiq,
an extremely potent narcotic, for ailments that have nothing to do with
its intended use. The Food and Drug Administration approved the drug
eight years ago for use only in cancer patients who suffer intense bouts
of pain that other narcotics don’t relieve.

In the first half of this year, oncologists, or cancer doctors,
accounted for only 1% of the 187,076 Actiq prescriptions filled at
retail pharmacies in the U.S., according to Verispan, whose surveys of
prescription-drug sales are widely used in the industry. Data gathered
from a network of doctors by research firm ImpactRx between June 2005
and October 2006 suggest that more than 80% of patients who use the drug
don’t have cancer. Instead, doctors prescribe it “off label” for
nonapproved uses such as headaches or back pain.

Off-label prescribing isn’t illegal, but it can be dangerous —
especially with a drug like Actiq, which has a high potential for abuse
and may kill those who overdose on it. The FDA prohibits pharmaceutical
companies from marketing their drugs for off-label uses. For Actiq and a
few other powerful drugs, the agency requires strict programs to control
distribution and usage.
MORE ON ACTIQ

• Read the full FDA risk-management program for Actiq (Adobe Acrobat
required)

Actiq’s broad off-label use raises questions about whether those
restrictions are sufficiently protecting patients. “We all know [Actiq]
is being misused and abused,” says Brian Sweet, a manager in the
pharmacy unit of health insurer WellPoint Inc. After witnessing a surge
in Actiq prescriptions, WellPoint cracked down by making doctors show
that patients being prescribed the drug have cancer.

Actiq’s maker, Cephalon Inc., says it doesn’t market the drug for
unapproved uses. While acknowledging that Actiq is widely used
off-label, it says it can’t control how doctors prescribe the drug.

Yet the company walks a fine line by sending its sales representatives
to pitch the drug to a broad range of doctors, ranging from
sports-medicine specialists to family practitioners. It gives these
doctors coupons for free samples. Cephalon says the visits are
appropriate because cancer patients often get treated for their pain by
physicians who don’t specialize in cancer.

Actiq contains fentanyl, a highly addictive substance about 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 opium, cocaine, methamphetamine and methadone. Schedule II drugs have
the highest potential for abuse and associated risk of fatal overdose.

Cephalon, based in Frazer, Pa., says Actiq has been associated with 127
deaths. Two of them involved children who confused the drug for candy.
Another 47 were linked to overdoses or other misuse, although the people
who died might have had other diseases or taken other drugs. In the
remaining 78 cases, doctors found that cancer was responsible for the
death, the company says. Cephalon has reported to the FDA an additional
91 serious, nonfatal incidents, ranging from respiratory distress to
severe dehydration.

The U.S. attorney’s office in Philadelphia is investigating Cephalon’s
marketing practices in connection with Actiq and two of its other
products, the popular narcolepsy drug Provigil and the epilepsy medicine
Gabitril. No charges have been filed.

Broader Crackdown

Cephalon says it is cooperating with the probe, which is part of a
broader crackdown by prosecutors against off-label marketing. In August,
the Justice Department fined Schering-Plough Corp. $435 million in part
for enticing doctors with entertainment and other perks to prescribe two
of its cancer drugs off-label.

Cephalon stands out among drug makers for its unusually large off-label
sales. Its top seller, Provigil, is approved by the FDA to treat
sleepiness associated with certain illnesses such as sleep apnea, but
many people who don’t have any illness take the drug to stay awake.
Analysts estimate about 80% of Provigil prescriptions are off-label.
Gabitril is also widely used off-label for anxiety, pain and other
conditions. Under FDA pressure, Cephalon last year curtailed its
marketing of the epilepsy drug because it was causing seizures in
patients without the disease, and sales dropped 23%.
[Successful Treatment]

Founded in 1987 by a former DuPont Co. scientist named Frank Baldino
Jr., Cephalon expects revenue to exceed $1.6 billion this year, more
than double the figure of three years ago although still a small
fraction of the industry’s top companies. Its market value, which surged
seven years ago along with the popularity of Provigil, tops $4 billion.
Dr. Baldino earned $2.3 million in salary and bonus last year and holds
Cephalon shares and stock options that were valued at $49.6 million as
of the end of last year.

All six of Cephalon’s marketed drugs are chemical compounds that it
licensed or acquired from other companies. Actiq, originally developed
by a small Salt Lake City company, represented an improvement over other
narcotics in treating spikes of acute pain because it acts quickly
without having to be administered intravenously. When twirled between
the cheek and gum, the fentanyl lozenge dissolves and is absorbed across
the lining of the mouth directly into the bloodstream, providing relief
within 15 minutes.

Actiq had sales of $15 million in 2000, when Cephalon acquired it. By
last year, sales had grown to $412 million, making it Cephalon’s No. 2
drug. In the first nine months of this year, sales jumped to $471
million. Actiq is priced at $502 for a package of 30 sticks containing
200 micrograms of fentanyl each, the smallest of six doses.

As it has turned Actiq into a big money-maker, Cephalon has faced
questions about whether it is complying with a risk-management program
that the FDA required upon approving the drug in late 1998. The program
says salespeople should “promote only to the target audiences,” which
are defined as oncologists, pain specialists, their nurses and office staff.

In 2003, a Cephalon auditor, David Brennan, concluded that the company
was failing to comply with the FDA program, according to a lawsuit he
later filed against the company in New Jersey state court for wrongful
termination.

An important provision of the program says Actiq’s maker should report
to the FDA every quarter whether “groups of physicians (such as a
particular specialty)” who represent “potential off-label usage greater
than 15%” are prescribing the drug. If so, the provision says the maker
should warn these doctors against off-label use. Mr. Brennan’s lawsuit
says that means Cephalon must act if all noncancer medical specialties
together account for more than 15% of prescriptions.

Cephalon interprets the provision differently. It says it only needs to
act if any individual specialty exceeds 15% of the total — and then
only if it can be shown that doctors in that specialty are prescribing
Actiq inappropriately. Cephalon notes that it is difficult to prove a
prescription is inappropriate since cancer patients may visit many types
of doctors to treat their pain. It believes the 15% clause has yet to be
triggered. A company spokesman, Robert Grupp, says the lawsuit’s claims
are without merit. The FDA declined to comment.

According to Verispan data for the first half of 2006, two specialties
exceed 15% of Actiq prescriptions: anesthesiologists at 29.5% and
physical medicine and rehabilitation specialists at 16%. The data show
oncologists and pain specialists account for less than 3% of
prescriptions. Cephalon doesn’t dispute the data.

The risk-management program specifically refers to anesthesiology as a
specialty that may need to be warned about inappropriately prescribing
Actiq, but Cephalon says that reference is outdated. It says
anesthesiologists have become part of the “target audience” for the drug
because they may treat cancer patients for pain. Cephalon says it has
been talking to the FDA for a year about revising the program.

After Mr. Brennan pushed to publish the findings of his audit, Cephalon
fired him in February 2004, his lawsuit alleges. Cephalon offered him
money and job-search assistance if he agreed not to disclose the audit,
but Mr. Brennan refused, the suit says. Mr. Grupp declined to discuss
Mr. Brennan’s dismissal but noted that he is “a former disgruntled
employee.”

Mr. Brennan has been interviewed twice by investigators working for the
U.S. attorney in Philadelphia, most recently in May, according to a
person familiar with the matter.

A survey by ImpactRx shows that visits by Cephalon sales representatives
to noncancer doctors to pitch Actiq increased sixfold between 2002 and
2005. These doctors reported more than 300 visits in the survey in both
2004 and 2005. Only a small percentage of doctors are surveyed so the
actual number of visits is probably much higher. Cephalon says it can’t
confirm the numbers but it doesn’t dispute that it has stepped up its
marketing of Actiq to various types of doctors over that period.

Stephen Leighton, a general practitioner in Winston-Salem, N.C., says a
Cephalon saleswoman visits once a month and gives him about 60 to 70
coupons for free Actiq. Patients can trade each coupon for six Actiq
sticks. Dr. Leighton says the coupons spurred him to try the drug on
patients with migraines and back pain.

Positive Experience

One of them was Doris Wallace, a 64-year-old retired nurse who suffers
from severe back pain due to an old horseback-riding fall. Ms. Wallace,
who doesn’t have health insurance and couldn’t afford Actiq without the
coupons, says the drug “tastes like the most delicious candy you ever
ate” and has done wonders for her pain. At the height of her use, she
was consuming 24 Actiq sticks a month.

The positive experience of patients like Ms. Wallace has led Dr.
Leighton to prescribe Actiq more widely for different types of pain.
Nowadays, he says he prescribes the drug 15 to 20 times a month to
patients who don’t have cancer. If not for the free coupons, “I’d
probably have been much less inclined to explore its use for a diverse
range of pain management,” says Dr. Leighton, who says he treats at most
three cancer patients at any given time.
[Diverse Market]

Dr. Leighton says he thinks the FDA-approved usage of Actiq is too
narrow. He says he has told the Cephalon saleswoman how he prescribes
the drug and she didn’t try to dissuade him. Mr. Grupp of Cephalon says
Dr. Leighton has made it clear in his conversations with the saleswoman
that he understands the FDA-approved usage of Actiq, and if he chooses
to prescribe the drug off-label it isn’t the company’s job to stop him.

Mr. Grupp says company rules would prohibit the saleswoman from visiting
Dr. Leighton only if he never prescribed the drug for cancer pain. “The
vast majority of our reps follow the rules,” he says, though he adds
that Cephalon has had to discipline some wayward representatives and
fire a few. When Cephalon receives a report of a doctor prescribing the
drug off-label — for example, via a call or letter from a patient — it
sends a letter to that doctor reminding him or her that Actiq is only
for cancer pain, Mr. Grupp says. The company has sent more than 3,300
such letters, he says.

Earlier this year, Dr. Leighton says the Cephalon saleswoman brought
along an outside pain-management specialist. Over lunch, Dr. Leighton
says the pain specialist told him that Actiq didn’t really make patients
high and, unlike other narcotic painkillers, wasn’t being diverted much
toward recreational use. Cephalon declined to comment on the conversation.

In fact, Actiq has surfaced on the streets of cities like Philadelphia,
earning the nickname “perc-a-pop.” Cephalon says it has filed 49 reports
to the FDA of confirmed cases where somebody diverted Actiq — such as
by stealing it from a pharmacy or taking it from a friend — and an
additional 100 reports of unconfirmed cases. Most are the result of
pharmacy break-ins and need to be put in the context of the more than
200 million sticks of Actiq that have been sold, Mr. Grupp says.

Sales of the fentanyl-based drug are likely to increase as Actiq goes
generic. In late September, Barr Pharmaceuticals Inc. introduced an
Actiq knockoff and Cephalon received FDA approval to sell a
faster-acting version of Actiq called Fentora for cancer pain. Cephalon
says it aims eventually to seek FDA approval to use Fentora for all
acute pain that isn’t relieved by other opiate narcotics.

Mrs. Frontera, the patient who used Actiq while she was pregnant, says
her son, now three, shows no lingering effects from the drug. Mrs.
Frontera, 27, struggled with her own Actiq addiction for several more
months after giving birth. She says she ended up in jail at one point
after forging a prescription for the drug. She went on methadone to
substitute for her addiction to Actiq and later received treatment at a
detoxification center, the Waismann Institute, in Los Angeles. Now she
lives in San Luis Obispo, Calif.

“It makes me angry that it was prescribed to me,” she says of Actiq. “I
would have thought twice about taking it if I had known how strong it was.”

Philip Delio, the neurologist who prescribed Actiq to Mrs. Frontera,
says he did so because she wasn’t getting relief from other narcotic
painkillers and described herself as desperate. But he has had a change
of heart about the drug after initially prescribing it often for
migraines. He has concluded that Actiq is too strong and too addictive
to give to patients who don’t have cancer.

Cephalon sales representatives still come by his Santa Barbara, Calif.,
office regularly. But Dr. Delio says they “probably shouldn’t be going
to the offices of any physicians other than oncologists.”

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