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Psoriasis Drug Guselkumab Shows Promise in Mid-Stage Trial

Human monoclonal antibody targets interleukin-23

In a new phase IIb trial, up to 86% of patients with moderate-to-severe plaque psoriasis receiving guselkumab (Janssen) achieved a physician’s global assessment (PGA) score of cleared psoriasis or minimal psoriasis at week 16, the study’s primary endpoint.

The study also showed significantly higher levels of efficacy for all doses of guselkumab at week 16 compared with the placebo group, and these responses were maintained through week 40. Further, the trial included an active-comparator arm, which showed that several guselkumab dosage regimens provided better response rates compared with the anti-tumor necrosis factor (TNF)-alpha agent adalimumab (Humira, Abbvie).

The findings were published in the New England Journal of Medicine.

Guselkumab is an investigational human monoclonal antibody that targets the protein interleukin-23. It is currently in phase III development as a subcutaneously administered therapy for the treatment of moderate-to-severe plaque psoriasis.

The X-PLORE trial was a randomized, placebo- and active comparator-controlled, parallel-group, dose-ranging study in which participants received subcutaneous injections of placebo, guselkumab (five dose groups: 5 mg at weeks 0 and 4, and then every 12 weeks; 15 mg every 8 weeks; 50 mg at weeks 0 and 4, and then every 12 weeks; 100 mg every 8 weeks; and 200 mg at weeks 0 and 4, and then every 12 weeks), or adalimumab (80-mg initial dose, followed by 40 mg every other week, starting 1 week after initial dose).

At week 16, significantly higher proportions of guselkumab-treated patients achieved a PGA score of 0 (cleared psoriasis) or 1 (minimal psoriasis) compared with patients receiving placebo across all dose groups: 34% (5 mg), 61% (15 mg), 79% (50 mg), 86% (100 mg), and 83% (200 mg) compared with 7% for placebo (P = 0.002 for 5 mg; P < 0.001 for all other doses).

According to major secondary endpoints, at week 16, significantly higher proportions of patients receiving guselkumab achieved at least a 75% or 90% improvement in the Psoriasis Area Severity Index (PASI 75 or PASI 90): 44% and 34%, respectively (5 mg); 76% and 34% (15 mg); 81% and 45% (50 mg); 79% and 62% (100 mg); and 81% and 57% (200 mg), compared with 5% and 2% for placebo (P < 0.001).

Complete clearance (PGA 0 and PASI 100) was observed in 62% and 54%, respectively, of patients in the guselkumab 100-mg group after 40 weeks of continuous treatment.

Guselkumab at doses of 50 mg, 100 mg, and 200 mg showed higher efficacy compared with that of the adalimumab treatment group. Significantly greater proportions of guselkumab-treated patients in the 50-mg (71%), 100-mg (77%), and 200-mg (81%) groups achieved a PGA score of 0 or 1 at week 40 compared with the adalimumab-treated group (49%).

Through week 16, the placebo-controlled period, adverse events (AEs) were reported in 50% of patients receiving guselkumab (combined groups), in 56% of patients receiving adalimumab, and in 52% of patients receiving placebo. Serious infections (appendicitis and lung abscess) occurred in two patients treated with guselkumab.

Between weeks 16 and 52, AEs were reported in 49% of patients receiving guselkumab (combined groups) and in 61% of patients receiving adalimumab. No additional serious infections occurred in guselkumab-treated patients, but one serious infection (pneumonia) occurred in a patient treated with adalimumab.

Source: Pipeline Review; July 8, 2015.

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