Washington Editor

SILVER SPRING, Md. - An expert advisory panel told the FDA Wednesday that it should approve Amgen Inc.'s Enbrel (etanercept) to treat moderate to severe plaque psoriasis in pediatric patients as young as 4 years.

The FDA's Dermatologic and Ophthalmic Drugs Advisory Committee voted 8 to 5 in favor of approval of Enbrel, a tumor necrosis factor (TNF) blocker, for pediatric patients with moderate to severe psoriasis.

More than half of the panelists said the 4 to 17 age group requested by Amgen, of Thousand Oaks, Calif., for the labeling was appropriate.

However, six of the advisers abstained from voting on the age group question; some saying there was not enough data to determine an appropriate age, while others were simply opposed to an age restriction for prescribing the drug in children.

Enbrel currently is approved in the U.S. to treat juvenile idiopathic arthritis in children as young as age 2.

However, the TNF blocker, which also is approved to treat moderate to severe psoriasis and rheumatoid arthritis in adults, has been linked to several serious and life-threatening adverse events, including serious infections, such as tuberculosis, histoplasmosis and coccidiodomycosis, and malignancies.

The FDA has received 949 adverse event reports in pediatric patients linked to Enbrel use, including 14 deaths. Amgen said it is aware of 16 deaths worldwide in the pediatric population associated with the drug's use.

Regulators announced June 4 that the agency is investigating the possible association between the use of TNF blockers and lymphoma and other cancers in children and young adults.

The FDA said it had received 30 reports since 1998 of cancer in children and young adults potentially linked to TNF inhibitors, such as Enbrel.

Nonetheless, the panel voted 7 to 5, with one abstention, that the drug's benefits outweigh its risks in treating children and adolescents with psoriasis.

Amgen said it is conducting a five-year ongoing extension study in 2,500 adults to evaluate the safety of the drug.

The results are expected in 2012.

Panelists voted 9 to 3, with one abstention, that its recommended approval should not wait for the completion of the safety study.

The committee debated about whether Enbrel should be limited to patients with only severe psoriasis rather than including moderate disease on the drug's labeling.

But several panelists objected, arguing that the diagnosis of severe psoriasis may depend not just on the percentage of the body affected by the disease but the location of the affected areas.

"A tiny bit of psoriasis in the wrong place," said panelist Lynn Drake, a physician at Massachusetts General Hospital in Boston, "can be debilitating."

Plaque psoriasis prominently affects the face and intertriginous areas in children, noted Lawrence Eichenfield, professor of pediatrics and dermatology at the University of California in San Diego.

Psoriasis, Eichenfield said, can have devastating physical and psychosocial effects on patients, especially for adolescents.

About 10 percent of patients with psoriasis contemplate suicide, said Mark Lebwohl, chairman of the medical board for the National Psoriasis Foundation.

Suicidal ideation is twice as high in adolescents with the disease, added Malia Lewin, of the International Psoriasis Council.

There currently are no approved systemic therapies to treat pediatric patients with the disease. However, physicians often prescribe drugs like methotrexate, cyclosporine or oral retinoids or ultraviolet B phototherapy.

Most children diagnosed with psoriasis do not have the severe form of the disease, and topical treatments generally are sufficient to control mild to moderate forms of the condition, said David Kettl, medical officer in the FDA's Division of Dermatology and Dental Products.

However, for those children and adolescents with severe psoriasis, topical treatments often are ineffective, Eichenfield said. In addition, he said, drugs like methotrexate and cyclosporine have toxic liver effects.

By not including moderate disease in the labeling, said Bruce Thiers, chairman of the dermatology service department at the Medical University of South Carolina in Charleston, insurers more than likely would restrict payments to only cover what they considered severe psoriasis.

Amgen officials declined to state an annual cost to pediatric patients for Enbrel. However, when pressed by one panelist, a representative at the firm admitted that the typical annual cost for an adult is $15,000 for the drug.

Analyst Eric Schmidt, of Cowen & Co., predicted that if approved for the pediatric population, Enbrel would gain a notable advantage in the increasingly competitive psoriasis market.

While the market opportunity for Enbrel in pediatric psoriasis is very modest, he said in a research note that "consultants believe Enbrel could gain a significant commercial advantage by becoming the only biologic in psoriasis with a label in children. They assert that community dermatologists who have yet to buy into biologics due to lingering safety concerns might be persuaded by such a label and differentially inclined to use Enbrel."

Thus, Schmidt said, he expects that Enbrel sales are likely to continue to grow in psoriasis because the market is expected to double over the next five years, and because the perception by dermatologists of its superior safety over other agents is enhanced by a label in pediatric psoriasis.

Schmidt surmised that Enbrel was unlikely to be challenged by Horsham, Pa.-based Centocor Inc.'s investigational psoriasis drug ustekinumab, a human monoclonal antibody that targets the cytokines interleukin-12 and interleukin-23.

The same FDA panel voted unanimously Tuesday in favor of approval of ustekinumab in adults with moderate to severe forms of the disease.

However, that panel also voted 7 to 4 for the injectable drug to be administered only in the physician office setting.

"Although our consultants are very optimistic that over time this could be the go-to biologic in psoriasis, the lack of long-term safety data and possible requirement for in-office administration . . . may restrict its use in the near term," Schmidt said.