Guselkumab demonstrates efficacy in plaque psoriasis
Phase 2b results show that blockade of IL-23 resulted in significant skin clearance, with improvements through week 40
SPRING HOUSE, Pa.―Results published in The New England Journal of Medicine from a Janssen Research & Development LLC-sponsored Phase 2b trial showed that up to 86 percent of patients with moderate to severe plaque psoriasis receiving guselkumab achieved a Physician’s Global Assessment (PGA) score of cleared or minimal psoriasis at week 16, the study’s primary endpoint.
The X-PLORE study showed significantly higher levels of efficacy for all guselkumab doses at week 16 when compared with the placebo group, and responses were maintained through week 40 of the study. The trial also included an active comparator arm, which showed that several guselkumab dosage regimens provided better response rates compared with the antitumor necrosis factor (TNF)-alpha agent, adalimumab (Humira). Guselkumab is an investigational human monoclonal antibody that targets protein interleukin (IL)-23 specific intracellular and downstream signaling, and is currently in Phase 3 development as a subcutaneously administered therapy for the treatment of moderate to severe plaque psoriasis.
Brian Kenney of Global Immunology & Biotechnology Pharmaceutical Communication & Public Affairs at Janssen tells DDNews, “Janssen R&D discovered and developed guselkumab, a monoclonal antibody with a novel mechanism of action that specifically targets interleukin-23, which is believed to play an important role in the pathogenesis of psoriasis and other immune-mediated diseases. Guselkumab is being initially studied for moderate to severe plaque psoriasis, to determine whether blockade of IL-23 alone can achieve high levels of complete skin clearance. Guselkumab is also being pursued for psoriatic arthritis and ulcerative colitis.”
X-PLORE is a Phase 2b, randomized, placebo- and active comparator-controlled, parallel-group, multicenter dose-ranging seven-arm study in which participants received subcutaneous injections of either placebo, guselkumab (five dose groups: 5 mg at weeks zero and four then every 12 weeks; 15 mg every eight weeks; 50 mg at weeks zero and four then every 12 weeks; 100 mg every eight weeks; and 200 mg at weeks zero and four then every 12 weeks) or adalimumab (80 mg initial dose, followed by 40 mg every other week starting one week after initial dose).
“The Phase 2b guselkumab study results show that blockade of IL-23 resulted in significant skin clearance, and improvements continued through week 40 with every eight- or 12-week maintenance treatment,” said study investigator Dr. Kristian Reich of Dermatologikum Hamburg in Germany. “These findings provide important insights into the role of IL-23 in the pathogenesis of psoriasis and the potential therapeutic benefit of guselkumab. Findings from the Phase 3 guselkumab studies will provide greater insights into the efficacy and safety profile of this novel monoclonal antibody.”
At week 16, significantly higher proportions of guselkumab-treated patients achieved PGA 0 (cleared psoriasis) or 1 (minimal psoriasis) compared with patients receiving placebo across all dose groups. According to major secondary endpoints, at week 16, significantly higher proportions of patients receiving guselkumab achieved at least a 75-percent or 90-percent improvement in the Psoriasis Area Severity Index (PASI 75 or PASI 90, respectively). Patients in all guselkumab groups achieved significantly greater decreases (improvement) in Dermatology Life Quality Index (DLQI) score from baseline to week 16 compared with placebo.
Guselkumab at doses of 50 mg, 100 mg and 200 mg showed higher efficacy when compared with the adalimumab treatment group. Significantly greater proportions of patients in the guselkumab 50 mg (79 percent), 100 mg (86 percent) and 200 mg (83 percent) groups achieved a PGA score of 0 or 1 at week 16 compared with the adalimumab group (58 percent). After week 16, the proportions of guselkumab-treated patients achieving a PGA score of 0 or 1, PASI 75 and PASI 90 remained consistent or showed additional improvement. Significantly greater proportions of guselkumab-treated patients in the 50 mg (71 percent), 100 mg (77 percent) and 200 mg (81 percent) groups achieved a PGA score of 0 or 1 at week 40 than the adalimumab-treated group (49 percent).
“In particular, substantial proportions of patients treated with guselkumab 100 mg every eight weeks achieved complete clearance through week 40, measured as PGA 0 (62 percent) and PASI 100 (54 percent). The Phase 3 clinical program is currently ongoing and consists of global programs that will evaluate guselkumab, including comparison with adalimumab and in patients who have had an inadequate response to Stelara,” continues Kenney.
Kenny adds, “We anticipate filing applications with health authorities in 2016 seeking approval of guselkumab for moderate to severe plaque psoriasis. It’s inappropriate to speculate on timing for guselkumab in terms of when it might be available for patients. We are excited about the potential of guselkumab as a next-generation biologic therapy, and what this treatment may mean for patients living with moderate to severe plaque psoriasis. We look forward to the Phase 3 study results in the future.”