12:00 AM
Jun 23, 2008
 |  BioCentury  |  Regulation

Enbrel: The subtext matters

An FDA advisory committee’s narrow vote to approve Enbrel etanercept to treat moderate-to-severe pediatric plaque psoriasis last week would have been much wider had the proposed indication been for severe disease only. The committee also recommended a stringent post-marketing plan for sponsor Amgen Inc.

FDA’s Dermatologic and Ophthalmic Drugs Advisory Committee voted 8-5 to recommend approval of the sBLA for Enbrel. If the agency listens to the bulk of the panel members’ comments, however, the drug will receive approval for severe disease only and Amgen will need to step up its post-marketing plans.

There was no question that Enbrel worked in the indication, with the committee voting 12-0 with one abstention that the drug demonstrated efficacy. What concerned the members were the risks associated with the soluble TNF receptor.

In March, Enbrel received a boxed warning for risk of infections, including bacterial sepsis and tuberculosis. The label also includes warnings that Enbrel has been associated with demyelinating disorders, malignancies, hematologic events and hepatitis B (HBV) reactivation. Amgen co-markets Enbrel for its approved indications in the U.S. and Canada with Wyeth, which holds rights elsewhere.

In debating the risk-benefit of Enbrel in pediatric psoriasis, panel members generally agreed there is a need for the drug and that common alternatives are more toxic.

Amgen presented data noting the decrease in quality of life caused by psoriasis, especially in the pediatric setting. Physically, chronic itching is unpleasant and can cause sleep disturbances, and plaques often bleed and can be debilitating. Furthermore, psoriasis can distort a patient’s self-image, which can have a more significant impact on children and adolescents than adults, as youth are in a critical period of psychosocial development.

Pediatric psoriasis patients report quality of life impairment worse than epilepsy and diabetes, but not quite as bad as chronic asthma, according to a 2006 study in the British Journal of Dermatology.

The most common treatments for psoriasis are topical corticosteroids and vitamin D analogs, which are typically given for two to four weeks. According to Lawrence Eichenfield, a professor of pediatrics and dermatology at the University of California at San Diegowho presented on behalf of Amgen at the meeting, those treatments are sufficient for most of the 60,000-110,000 pediatric moderate-to-severe plaque psoriasis patients in the U.S.

However, he said there is a subset that does not respond to those medications. These patients often receive systemic therapies that are approved for adults but not for children.

The most common of these off-label treatments is ultraviolet B radiation (UVB). But “getting kids 10 years old or younger into a box is extremely difficult,” said non-voting industry representative Ellen Strahlman, VP of worldwide business development at Pfizer Inc.

Other off-label treatments include methotrexate, cyclosporine, retinoids and biologics such as Enbrel and the anti-TNF antibodies Remicade infliximab from Johnson & Johnson and Schering-Plough Corp. and Humira adalimumab from Abbott Laboratories.

Remicade is...

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