Centocor, Inc (HORSHAM, Pennsylvania), announced that findings from a phase III multicenter, randomized head-to-head study comparing ustekinumab and Enbrel^® (etanercept) for the treatment of moderate-to-severe psoriasis showed ustekinumab to be superior according to primary and major secondary efficacy endpoints. The ACCEPT phase III study included 903 patients with chronic plaque psoriasis (etanercept = 347, ustekinumab 45 mg = 209, ustekinumab 90 mg = 347). The primary endpoint was the percentage of participants achieving at least a 75% reduction in psoriasis at week 12 as measured by the Psoriasis Area and Severity Index (PASI 75). At week 12, after two subcutaneous injections at weeks 0 and 4, a total of 68% and 74% of patients receiving ustekinumab 45 mg (P = .012) or ustekinumab 90 mg (P <.001), respectively, achieved a PASI 75 compared with 57% of patients receiving Enbrel 50 mg subcutaneous injections twice-weekly for 12 weeks.

The study also demonstrated that patients receiving ustekinumab achieved higher marked improvements in psoriasis as assessed by PASI 90 improvement and Physician Global Assessment scores versus patients receiving Enbrel, major secondary endpoints of the trial. At week 12, a total of 36% of patients receiving ustekinumab 45 mg and 45% of patients receiving ustekinumab 90 mg achieved PASI 90 versus 23% of patients receiving Enbrel (P <.001 for each comparison vs Enbrel). Moreover, a greater proportion of patients in the ustekinumab 45 mg and 90 mg treatment groups achieved a PGA score of "cleared" or "minimal" (65% and 71%, respectively) compared with Enbrel-treated patients (49%) (P <.001 for each comparison).

Through week 12 of the comparator-controlled portion of the study, the percentage of participants experiencing at least one adverse event (AE) were comparable among all three groups: 1.9% and 1.2% of patients receiving 45 mg or 90 mg ustekinumab, respectively, compared with 1.2% of patients receiving Enbrel. AEs leading to treatment discontinuation occurred in 1.9% and 1.2% of patients in the ustekinumab 45 mg and 90 mg groups, respectively, compared with 2.3% of patients treated with Enbrel. Rates of specific AEs included injection site erythema, which was reported in 14.7% of subjects treated with Enbrel versus 0.7% of subjects in the combined ustekinumab groups, though this disparity may have been influenced by the greater number of Enbrel injections required (up to 48 in the 12-week study) compared with two ustekinumab injections.

Ustekinumab, a human monoclonal antibody targeting the cytokines interleukin-12 and -23, is being investigated as an infrequently self-administered subcutaneous injection. The US FDA has extended the drug’s review timeline for the Biologic License Application by 3 months to December 2008 to provide additional time for review of application amendments provided by Centocor. The FDA has requested no additional clinical trials. The FDA's Dermatologic and Ophthalmic Drugs Advisory Committee unanimously recommended ustekinumab for approval. The Marketing Authorization Application for ustekinumab was submitted by Janssen-Cilag International NV in Europe and is currently under review by the European Medicines Agency. Centocor discovered ustekinumab and has exclusive marketing rights to the product in the US. Janssen-Cilag companies have exclusive marketing rights in all countries outside of the US. Centocor and the Janssen-Cilag companies are members of the Johnson & Johnson family of companies.