The Janssen Pharmaceutical Companies of Johnson & Johnson announced 24-week Phase 3 data showing a significantly greater proportion of patients with active psoriatic arthritis (PsA) treated with TREMFYA® (guselkumab) achieved at least a 20 percent improvement in disease signs and symptoms (American College of Rheumatology ACR20 response) compared to placebo. These findings represent the primary endpoints of the DISCOVER-1 and DISCOVER-2 Phase 3 studies, which were designed to evaluate the efficacy and safety of investigational use of TREMFYA for the treatment of adult patients with active PsA.
"People living with psoriatic arthritis cope with symptoms like pain, joint swelling and irreversible joint damage that may interfere with their daily activities," said Atul Deodhar, MD, MRCP, FACP, FACR, Professor of Medicine, Oregon Health & Science University and study steering committee member.* "These data show TREMFYA as a potential treatment option to help patients living with this serious disease."
The data presented at ACR are the first Phase 3 study results in active PsA evaluating a human monoclonal antibody against the p19 subunit of IL-23. DISCOVER-1 evaluated 381 participants with active PsA who had an inadequate response to standard therapies, including participants previously treated with anti-tumor necrosis factor (TNF) alpha biologics. DISCOVER-2 evaluated 739 participants with active PsA who were biologic-naive and had an inadequate response to standard therapies.
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Results from DISCOVER-1 show that at week 24, 59 percent of adult patients with active PsA receiving TREMFYA every four weeks (q4w) and 52 percent of patients receiving TREMFYA at weeks 0, 4 and every eight weeks thereafter (q8w) achieved an ACR20 response compared to 22 percent of patients receiving placebo (both p<0.001). Among patients who had a ≥3 percent body surface area (BSA) affected with psoriasis, and an Investigator Global Assessment (IGA) score of ≥2 at baseline, 75 percent of patients receiving TREMFYA q4w and 57 percent of patients receiving TREMFYA q8w achieved an IGA score of 0 (cleared) or 1 (minimal) and a >2 grade reduction, compared to 15 percent of patients receiving placebo (both p<0.001).
Results from DISCOVER-2 show that at week 24, 64 percent of adult, biologic-naive patients with active PsA receiving TREMFYA q4w or q8w respectively, achieved an ACR20 response, compared to 33 percent of patients receiving placebo (both p<0.001). Among patients who had a ≥3 percent BSA affected with psoriasis, and an IGA score of ≥2 at baseline, 69 percent receiving TREMFYA q4w and 71 percent receiving TREMFYA q8w achieved an IGA score of 0 or 1, and a ≥2 grade reduction from baseline, compared to 19 percent of patients receiving placebo (both p<0.001). Patients with active PsA receiving TREMFYA q4w showed significantly reduced radiographic damage progression vs. placebo at week 24.
In DISCOVER-1 and DISCOVER-2, observed adverse events (AEs) were generally consistent with previous studies of TREMFYA and current prescribing information.
Data from the DISCOVER program formed the basis of the September 13, 2019 supplemental Biologics License Application submission to the U.S. Food and Drug Administration (FDA) for approval of TREMFYA and the validated filing on October 11, 2019 to the European Medicines Agency (EMA) for approval of TREMFYA in the European Union for adult patients with active psoriatic arthritis.
"We are passionate about the development of therapies, such as TREMFYA, since patients are still struggling with active psoriatic arthritis and need new treatment options," said Alyssa Johnsen, MD, PhD, Vice President, Rheumatology Disease Area Leader, Janssen Research & Development. "These results from the DISCOVER program represent a major step in the development of TREMFYA as a treatment for psoriatic arthritis."
The DISCOVER studies also evaluated multiple secondary endpoints, including ACR50/70 response, resolution of soft tissue inflammation (enthesitis and dactylitis), disease activity (DAS-28 CRP), improvement in physical function (HAQ-DI), and general health outcomes (SF-36 PCS and MCS).
DISCOVER-1 is a randomized, double-blind, multicenter Phase 3 study evaluating the efficacy and safety of TREMFYA administered by subcutaneous injection in participants with active psoriatic arthritis including those previously treated with biologic anti-TNF alpha agent(s). DISCOVER-1 is evaluating 381 participants and continuing through approximately one year.
The study consists of: a screening phase of up to six weeks, a blinded treatment phase of 52 weeks that includes a placebo-controlled period from week 0 to week 24 and an active treatment period from week 24 to week 52, and a safety follow-up phase of eight weeks after week 52 (week 52 to 60; 12 weeks from the last administration of study agent [at week 48] through to the final visit in the safety follow-up phase). Efficacy, safety, pharmacokinetic, immunogenicity and biomarker evaluations are being performed in the study on a defined schedule.
DISCOVER-2 is a randomized, double-blind, multicenter Phase 3 study evaluating the efficacy and safety of TREMFYA administered by subcutaneous injection in subjects with active psoriatic arthritis. DISCOVER-2 is evaluating 739 participants and continuing through approximately two years.
The study consists of: a screening phase of up to six weeks, a blinded treatment phase (approximately 100 weeks) that includes a placebo-controlled period from week 0 to week 24 and an active treatment period from week 24 to week 100, and a safety follow-up phase of 12 weeks after the last administration of study agent. Efficacy, health economics, safety, pharmacokinetics, immunogenicity, biomarker and pharmacogenomics evaluations are being performed in the study on a defined schedule.
Psoriatic arthritis (PsA) is a chronic, immune-mediated inflammatory disease characterized by peripheral joint inflammation, enthesitis, dactylitis, axial disease, and the skin lesions associated with psoriasis. Studies show that up to 30 percent of people with psoriasis also develop psoriatic arthritis. The disease causes pain, stiffness and swelling in and around the joints; it commonly appears between the ages of 30 and 50, but can develop at any time. Though the exact cause of PsA is unknown, genes, the immune system and environmental factors are all believed to play a role in the onset of the disease.
Developed by Janssen, TREMFYA® is a human monoclonal antibody against the p19 subunit of interleukin (IL)-23, and is approved in the U.S., Canada, the European Union, Japan and a number of other countries worldwide for the treatment of adult patients with moderate to severe plaque psoriasis who may benefit from taking injections or pills (systemic therapy) or phototherapy (treatment using ultraviolet [UV] light). IL-23 is an important driver of the pathogenesis of inflammatory diseases such as psoriasis and psoriatic arthritis.