Ustekinumab approval delayed by FDA

Skin & Allergy News, Feb, 2009 by Elizabeth Mechcatie

The Food and Drug Administration has requested more information about ustekinumab before it is approved for treating moderate to severe plaque psoriasis, according to Centocor Inc., the manufacturer of the monoclonal antibody.

In a statement issued in December, the company reported that the information requested by the FDA includes a proposal for a Risk Evaluation and Mitigation Strategy (REMS) to ensure that the product's benefits outweigh its risks.

The REMS is used to manage a potential or known serious risk associated with a drug or biological product, which the FDA can require a company to establish if it is considered necessary.

The REMS must include a medication guide, a patient information pamphlet to be provided with each prescription (including refills), and a communication plan, but does not require restricted distribution of the drug, according to Centocor. The FDA is not requesting any new studies on the efficacy and safety of ustekinumab before it is approved.

The FDA outlined its requests in a Complete Response Letter, which indicated that the review for the application has been completed but the product is not ready to be approved. Such letters have replaced the "approvable" or "nonapprovable" letters issued to manufacturers in the past.

The FDA does not release information about complete response letters, but the manufacturers are at liberty to do so.

In June 2008, the FDA's dermatologic and ophthalmic drugs advisory panel recommended approval of ustekinumab for psoriasis in an 11-0 vote.

The panel also unanimously agreed that more safety data in more patients treated for a longer period of time were critical, and that the potential for malignancies associated with ustekinumab was based on the theoretical risk as well as some data indicating an increased carcinogenic risk associated with blocking IL-12 in mice.

The panel agreed that the manufacturer's postmarketing plans to evaluate the long-term risks of ustekinumab were not adequate ("Ustekinumab for Psoriasis Wins Backing of Panel," July 2008, pg. 1).

If approved, ustekinumab would be the sixth biologic therapy approved for psoriasis.

Ustekinumab is thought to work by preventing the cytokines interleukin-12 (IL-12) and interleukin-23 (IL-23) from differentiating and activating T helper (Th)1 and Th17 cells, "'thereby inhibiting key pathways implicated in the immunopathogenesis of psoriasis," according to the company.

BY ELIZABETH MECHCATIE

Senior Writer