information: Presentation of results at a congress
Announcement: presentation of results at the 2018 American Academy of Dermatology (AAD) Annual Meeting
Company: Janssen Research & Development, a J&J company (USA - NJ)
Product: guselkumab (CNTO 1959)
- monoclonal antibody. Guselkumab is a human monoclonal antibody that targets interleukin (IL)-23, and is in Phase 3 clinical development as a subcutaneously administered therapy for the treatment of moderate to severe plaque psoriasis.
- This antibody was generated utilizing the HuCAL antibody library technology licensed from MorphoSys.
area: Autoimmune diseases - Dermatological diseases
Country: Australia, Canada, Czechia, Germany, Republic of Korea, Poland, Russian Federation, Spain, USA
- The Phase 3 VOYAGE 2 trial is a randomized, double-blind, placebo- and active-comparator controlled study with randomized withdrawal and retreatment from weeks 28 to 76, data that will be presented in the future. The trial is designed to evaluate the safety and efficacy of guselkumab compared with placebo and adalimumab and of guselkumab maintenance therapy compared with withdrawal of therapy in adult patients with moderate to severe plaque psoriasis. Patients (n=992) were randomized to receive subcutaneous (SC) injections of guselkumab 100 mg at weeks 0, 4, 12 and 20; placebo at weeks 0, 4, and 12 with crossover to guselkumab at weeks 16 and 20 or adalimumab 80 mg at week 0, followed by 40 mg at week 1 and every two weeks through week 23. (NCT02207244)
- • On February 16, 2018, Janssen announced today new data that showed a vast majority of patients with moderate to severe plaque psoriasis receiving Tremfya® (guselkumab) who achieved at least 90 percent improvement in the Psoriasis Area and Severity Index (PASI 90) at week 28, maintained a PASI 90 response with continuous treatment through week 72. Findings from the study also demonstrated that a vast majority of patients originally randomized to Tremfya® , but withdrawn from treatment at week 28, regained a PASI 90 response within six months of initiating Tremfya® retreatment. These long-term findings from the Phase 3 VOYAGE 2 study have been presented at the 2018 American Academy of Dermatology (AAD) Annual Meeting. Results from the trial demonstrated that among patients who achieved PASI 90 response at week 28 with Tremfya®, 86 percent who continued receiving Tremfya® maintained a PASI 90 response through week 72, while only 11.5 percent of patients who were withdrawn from treatment maintained PASI 90 response. Of 173 patients who lost PASI 90 response after withdrawal from Tremfya®, 87.6 percent recaptured PASI 90 response six months following re-treatment. No new safety signals were observed with continuous treatment or retreatment therapy with Tremfya® through week 100.
- • On March 3, 2017, Janssen Research & Development announced new findings from two pivotal Phase 3 studies reporting the efficacy and safety of guselkumab in the treatment of adults with moderate to severe plaque psoriasis. Data from the VOYAGE 2 study showed that patients treated with guselkumab experienced significant improvements in skin clearance and other measures of disease activity compared with placebo, and significantly greater improvements compared with the anti-tumor necrosis factor (TNF)-alpha treatment Humira® (adalimumab). VOYAGE 2 is the second Phase 3 study to demonstrate superior efficacy of guselkumab versus adalimumab following VOYAGE 1. Data from a third Phase 3 study (NAVIGATE) showed that patients who had an inadequate response following treatment with the anti-interleukin (IL)-12/23 monoclonal antibody (mAb) STELARA® (ustekinumab) and who then switched to guselkumab, showed significantly greater improvements in skin clearance compared with patients who continued to receive STELARA®. These Phase 3 data are being presented at the 2017 American Academy of Dermatology (AAD) Annual Meeting in Orlando, FL, March 3-7.
- VOYAGE 2: Efficacy and safety of guselkumab compared with adalimumab for the treatment of moderate to severe plaque psoriasis
In the VOYAGE 2 study, the co-primary endpoints were met at week 16, with 84.1 percent of patients receiving guselkumab 100 mg at weeks 0 and 4 and then every 8 weeks achieving an Investigator’s Global Assessment (IGA) score of cleared (0) or minimal (1) disease compared with 8.5 percent of patients receiving placebo (P < 0.001). In addition, 70.0 percent of patients receiving guselkumab achieved a Psoriasis Area Severity Index (PASI) 90 score (near complete skin clearance) compared with 2.4 percent of patients receiving placebo (P < 0.001).
- Major secondary endpoints in VOYAGE 2 achieved statistical significance in comparisons of guselkumab versus adalimumab administered subcutaneously at weeks 0 (80 mg), 1 (40 mg) and then 40 mg every other week (all P < 0.001). At week 16, following three injections of guselkumab and ten injections of adalimumab, significantly higher proportions of patients receiving guselkumab versus adalimumab achieved IGA 0/1 (84.1 percent versus 67.7 percent, respectively) and PASI 90 (70.0 percent versus 46.8 percent, respectively). Guselkumab continued to demonstrate superiority versus adalimumab at week 24 for both the IGA 0/1 and PASI 90 scores. Among other secondary endpoints, significantly higher proportions of patients receiving guselkumab compared with adalimumab achieved Dermatology Life Quality Index (DLQI) scores of 0/1 (indicating no impact of psoriasis on health-related quality of life) and PASI 100 scores (complete skin clearance) at week 24. Additionally, at week 16 and 24, 34.1 percent and 44.2 percent of patients receiving guselkumab achieved PASI 100 responses, respectively.
- “The majority of patients treated with guselkumab achieved high levels of skin improvement (more than 80 percent IGA 0/1 and nearly 70 percent PASI 90) at week 16, while this was rarely seen in patients receiving placebo (less than 10 percent); a difference that was highly significant. Higher rates in efficacy in major secondary endpoints comparing guselkumab with adalimumab were also demonstrated and significant,” said Kristian Reich, Ph.D., M.D., Dermatologikum Hamburg, VOYAGE 2 study investigator. “These findings are consistent with the previously presented Phase 3 VOYAGE 1 study results and further demonstrate the important role of selectively targeting IL-23 in an immune-mediated disease like plaque psoriasis.”
- Through week 16, the placebo-controlled period, 44.8 percent, 47.6 percent and 48.4 percent of patients receiving placebo, guselkumab and adalimumab, respectively, reported at least one adverse event (AE). Serious AEs were reported in 1.2 percent of patients receiving placebo, 1.6 percent of patients receiving guselkumab and 2.4 percent of patients receiving adalimumab. Serious infections occurred in one patient receiving placebo, one patient receiving guselkumab and two patients receiving adalimumab. During this period, no malignancies were reported, and one major adverse cardiovascular event (MACE) was reported (in the adalimumab group).
- Through week 28, the active comparator period, patients receiving guselkumab (58.3 percent) and adalimumab (62.9 percent) reported at least one AE. Serious AEs were reported in 3.6 percent of patients receiving guselkumab and 3.6 percent of patients receiving adalimumab. Infections and infections requiring treatment were also comparable between guselkumab and adalimumab groups. Three serious infections each were reported in the guselkumab (bronchitis, erysipelas and soft-tissue infection) and adalimumab (2 cases of tuberculosis [1 disseminated] and 1 injection-site abscess) groups. One malignancy of prostate cancer in the guselkumab group and 2 non-melanoma skin cancers (1 squamous cell carcinoma in the guselkumab group and 1 basal cell carcinoma in the placebo to guselkumab group) were reported. Two major adverse cardiovascular events (MACE) were reported (1 myocardial infarction each in the guselkumab and adalimumab groups). There were no deaths.