1/1/05 Skin & Allergy News 1
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`Skin & Allergy News
`Copyright 2005 International Medical News Group
`January 1, 2005
`Volume 36; Issue 1
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`Mandatory FDA restrictions on the way for isotretinoin: voluntary programs deemed ineffective.
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`Kirn, Timothy F.
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`The Food and Drug Administration will scrap isotretinoin's handful of voluntary risk
`management programs in favor of one mandatory, more restrictive system like that used for
`thalidomide.
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`Although many dermatologists are relieved that isotretinoin won't be removed from the market,
`some expressed concern that the FDA's decision may prompt more dermatologists to stop
`prescribing the teratogenic ache drug--and could push patients to seek the drug from sources on
`the Internet.
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`"In the long run, this [policy] is short sighted," said Hilary Baldwin, M.D., vice chair of
`dermatology at the State University of New York, Brooklyn. "'I'm just very sad."
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`The new program is expected to go into effect this year. Prescribing physicians, dispensing
`pharmacies, and patients will be required to register in a program known as RiskMAP (risk
`minimization action plan). This program will be run by the drug-development services company
`Convance Inc., which has contracted with Roche, the manufacturer of Accutane, as well as with
`the manufacturers of generic isotretinoin.
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`The Nov. 23 announcement came the week after a senior FDA official--during a Senate hearing
`on the abrupt recall of the COX-2 inhibitor Vioxx because of reports linking it to cardiovascular
`events--named isotretinoin as one of five drugs that ought to be either withdrawn from the
`market or more severely restricted.
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`The close timing of the FDA's announcement and the well-publicized Senate testimony may
`have been coincidence, however. In a statement, the FDA said it was able to make the
`announcement now because an agreement was reached with Celgene Corp., which owns a patent
`on the STEPS (System for Thalidomide Education and Prescribing Safety) program, on which
`the isotretinoin program will be based.
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` A
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` more restrictive risk management program had been expected since March 2004, when two
`FDA advisory committees concluded that Roche's SMART (System to Manage Accutane
`Related Teratogenicity) program and similar programs for generic isotretinoin had failed to pre
`vent pregnancy exposures (SKIN & ALLERGY NEWS, April 2004, p. 1).
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`At the meeting of those committees, data were presented that showed 127 pregnancy exposures
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`CELGENE EXHIBIT 2016
`Coalition for Affordable Drugs VI LLC (Petitioner) v. Celgene Corporation (Patent Owner)
`Case IPR2015-01103
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`Page 1 of 3
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`occurred in the year before the SMART program was implemented, compared with 120
`pregnancy exposures in the year after, despite the fact that isotretinoin prescriptions declined by
`23%.
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`Moreover, when the SMART program and the others were approved by FDA, the agency had
`threatened that further restrictions would be imposed unless 60% of women who were written a
`prescription enrolled in a voluntary, ongoing survey run by the manufacturers. That goal was not
`met.
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`The Shape of Restrictions to Come
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`Under RiskMAP, the following conditions must be met before isotretinoin can be dispensed:
`documentation of patient education by the provider; a signed informed-consent form; and a
`negative pregnancy test, which will have to be repeated in order for the patient to obtain refills.
`More specific details of the program have yet to be determined.
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` A
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` major advantage of the new program is that physicians will no longer have to ad here to the
`requirements of four similar but distinct programs, each run by different manufacturers. Some
`physicians found that confusing, the FDA said. Instead, there will be a single, unified program
`covering all brands of isotretinoin.
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`In contrast to what has occurred under the isotretinoin risk management programs, pregnancy
`exposures to thalidomide have been well controlled under the STEPS program. About 4,000
`women of childbearing age have taken thalidomide since it was reintroduced into the market for
`the treatment of cancer and leprosy. Only one pregnancy exposure has occurred, resulting in a
`spontaneous abortion.
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`The official response to the FDA action from the American Academy of Dermatology was one
`of relief that there is no plan to withdraw isotretinoin from the market.
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`"Let me assure you that isotretinoin has not been taken off the market as a result of this [Senate]
`hearing: it will continue to be available for your patients," stated AAD President Boni E. Elewski,
`M.D., in a letter mailed to academy members.
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`The letter notes that the academy is being given an active role in designing the new program, and
`it urges dermatologists to remain conscientious about fulfilling the present prescribing program
`requirements because it is a time of increased 'scrutiny."
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`Dermatologists write 80% of the prescriptions for isotretinoin.
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`Unofficially, however, some dermatologists contacted by this newspaper were chagrined. "It's
`unfortunate," said Alan R. Shalita, M.D., professor and chair of dermatology at the State
`University of New York, Brooklyn, and an acne researcher. "We'll just have to live with
`whatever restrictions they impose."
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`Dr. Shalita's colleague, Dr. Baldwin, said she too thought the new program would mean that
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`fewer physicians would be willing to prescribe isotretinoin. That will probably drive patients to
`the Internet to get their medication, she added, leaving more patients without any medical
`supervision at all.
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`There are more than 30 brands of isotretinoin made and sold worldwide, she noted.
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`"I'm also worried that they are going to get 'Pete's" isotretinoin, and it is not even going to have
`isotretinoin in it," she said.
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`Thalidomide may not have had as many pregnancy exposures as isotretinoin, but that does not
`necessarily mean the thalidomide program will work the same way for isotretinoin, Dr. Baldwin
`said.
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`Most patients treated with thalidomide are older, and they are being treated for multiple
`myeloma. Therefore, they are very sick and probably not inclined to have sexual intercourse.
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`The FDA's action also prompted a statement from Rep. Bart Stupak (D-Mich.), a well-known
`critic of isotretinoin, whose son committed suicide while taking the drug.
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`Stupak's statement suggested that the wrangling over isotretinoin may continue. The
`congressman vowed to respond if the FDA's final risk management program was not strict
`enough, and he called for hearings specifically on isotretinoin.
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` DATA WATCH Isotretinoin Prescribing Declines 1999 1.9 2000 2.0 2001 1.6 2002 1.3
` 2003 1.2 Note: table made from line graph. Note: Based on data for more than 2 billion phar
`macy, hospital, and medical transactions per year in the United States, Source: Verispan
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