TNF class impacted?

National report - Experts disagree on the possible impact a new pediatric cancer warning for tumor necrosis factor (TNF) inhibitors may have on this drug category's growth.

Douglas Kress, M.D., chief of pediatric dermatology, Children's Hospital of Pittsburgh, says the new warnings mandated by the Food and Drug Administration (FDA) will significantly crimp the TNF-blocker drug class.

"This warning, coming almost immediately after Raptiva's (efalizumab) worldwide withdrawal by Genentech, is going to be a significant hit to the market. It's not going to go well for biologic drugs in the next year," he says.

Because no TNF blockers hold FDA approval for any pediatric indications in dermatology, she adds, "There are no prescribing patterns to impact."

Should a TNF blocker gain U.S. pediatric approval, however, the warning would be "consistent with the cautious approach already in place among dermatologists," she says.

Etanercept

Presently, only Amgen/Wyeth, manufacturer of Enbrel (etanercept), has applied for a pediatric psoriasis indication, but this application is stalled in preregistration, Ms. Kim says.

The FDA's Dermatologic and Ophthalmic Drug Advisory Committee reviewed the application last summer, and recommended approval only for severe pediatric psoriasis - not moderate-to-severe psoriasis, as Wyeth, she says.

Amy S. Paller, M.D., professor and chairman of dermatology and professor of pediatrics, Northwestern University Feinberg School of Medicine, Chicago, says the cancer warning could make it more difficult for etanercept to earn approval for pediatric psoriasis - and it might discourage manufacturers from testing other TNF inhibitors in children.

Etanercept ranks as the most popular TNF blocker, with 2007 U.S. sales of $662 million and a projected $850 million in 2012, Ms. Kim says.

Overall, she says sales of TNF blockers in the United States reached $829 million in 2007, versus $302 million total in other major markets (France, Germany, Italy, Spain, England and Japan). For 2012, Decision Resources predicts $1.4 billion in U.S. sales and approximately $670 million in sales in other major markets.

Ustekinumab approved

Competitors to TNF blockers now will include Stelara (ustekinumab, Centocor/Johnson & Johnson), which won FDA approval Sept. 25.

Ms. Kim says Stelara "should be a very good challenger to the TNF drugs. Dermatologists are very enthusiastic about ustekinumab because of its efficacy, and because it's dosed every 12 weeks."

Joel M. Gelfand, M.D., M.S.C.E., says ustekinumab will be "an alternative treatment option for patients."

However, "It certainly doesn't have the long-term safety record that the TNF inhibitors do," says Dr. Gelfand, medical director, clinical studies unit, and associate professor of dermatology at the University of Pennsylvania, Philadelphia.

Alan Menter, M.D., chairman, division of dermatology, Baylor University Medical Center, Dallas, adds that because only 3,000 patients have taken ustekinumab, "I don't believe ustekinumab will suddenly become the drug of choice" due to the new TNF-blocker warnings.

Going forward, Dr. Menter says, "Everybody is going to have to be more cautious, which is good."

Disclosures: Dr. Kress is a consultant and speaker for Amgen. Dr. Gelfand is a consultant and investigator for various manufacturers of biologic drugs for psoriasis including Amgen, Centocor and Abbott. Dr. Menter has performed clinical research for Amgen, Centocor and Abbott, but owns no stock in these companies. Dr. Paller is an investigator for Amgen and a consultant for Abbott and may become a consultant (without honorarium) for Centocor. Ms. Kim reports no relevant financial interests.