Janssen's First-in-Class TREMFYA (guselkumab) Approved by European Commission for Active Psoriatic Arthritis

Compiled by Keke

On November 25, Janssen Pharmaceuticals, a subsidiary of Johnson & Johnson, announced that the European Commission (EC) had approved TREMFYA (guselkumab) for the treatment of adult patients with active psoriatic arthritis (PsA) who have had an inadequate response to or are intolerant of prior disease-modifying antirheumatic drug (DMARD) therapy. Following initial doses at Week 0 and Week 4, guselkumab is administered as a 100 mg subcutaneous injection every 8 weeks; for PsA patients at high risk of joint damage, a 100 mg subcutaneous injection every 4 weeks may be used based on clinical judgment.

Janssen introduced that guselkumab is the first fully human monoclonal antibody approved to selectively bind to the p19 subunit of interleukin (IL)-23 and inhibit its interaction with the IL-23 receptor. The drug has been approved for the treatment of patients with moderate-to-severe plaque psoriasis.

The approval of this new indication is based on the results of the Phase 3 clinical studies DISCOVER-1 and DISCOVER-2, which evaluated the safety and efficacy of guselkumab 100 mg administered every 4 weeks (q4w) and every 8 weeks (q8w) in adult patients with active psoriatic arthritis (PsA). DISCOVER-1 enrolled 381 patients with active PsA who had an inadequate response to standard therapy, including those previously treated with anti-tumor necrosis factor (TNF)-α biologics (approximately 30%). DISCOVER-2 enrolled 739 patients who were biologic-naïve and had an inadequate response to standard therapy. The results of both studies demonstrated:

At Week 24, the American College of Rheumatology 20% improvement (ACR20) response in adult patients with active psoriatic arthritis (PsA) treated with guselkumab every 4 weeks (q4w) and every 8 weeks (q8w) (DISCOVER-1: n=255; DISCOVER-2: n=493) reached statistical significance compared with the placebo group (DISCOVER-1: n=126; DISCOVER-2: n=246) (DISCOVER-1: p<0.001; DISCOVER-2: p<0.001), thereby meeting the primary endpoint.

Furthermore, in DISCOVER-1, patients in the guselkumab groups demonstrated significant improvements in quality of life scores (36-item Short Form [SF-36] Physical Functioning score) compared with the placebo group (p<0.001 for both dose groups); in DISCOVER-2, patients in the q4w guselkumab group showed significant improvements in quality of life scores compared with the placebo group (p=0.0056 [q8w, p=0.068]).

In DISCOVER-2, the inhibition of structural damage progression was assessed radiographically and expressed as the mean change from baseline in the modified van der Heijde–Sharp (vdH-S) score. At Week 24, radiographic progression of structural damage was significantly less in the guselkumab q4w group than in the placebo group (p=0.006), whereas the guselkumab q8w group showed a numerically lesser degree of structural damage progression compared with the placebo group (p=0.068). At Week 52, the mean changes from baseline in the total modified vdH-S score were similar for the guselkumab q8w and q4w groups (mean scores of 0.97 and 1.07, respectively).

Furthermore, compared with the placebo group, the q4w and q8w guselkumab groups demonstrated higher Psoriasis Area and Severity Index 75% improvement (PASI 75), as well as higher PASI 90 and PASI 100 response rates (in DISCOVER-1, p=0.0005 for PASI 100, with all unadjusted p<0.001; in DISCOVER-2, all unadjusted p<0.001).

In both studies, guselkumab was well tolerated, and the observed adverse events (AEs) were generally consistent with previous studies of guselkumab and its current prescribing information. In DISCOVER-1 and -2, the rates of serious adverse events in the q4w treatment groups (0% and 3%) and the q8w treatment groups (3% and 1%) were similar to those in the placebo group (4% and 3%). In DISCOVER-2, less than 1% of patients experienced serious infections after receiving guselkumab, whereas no patients in DISCOVER-1 experienced serious infections following guselkumab treatment. There were no reports of death among patients treated with guselkumab, and no patients receiving guselkumab developed inflammatory bowel disease, opportunistic infections (such as tinea or candidiasis), active tuberculosis, or allergic or serum sickness-like reactions.

Reference source: European Commission Approves Janssen’s TREMFYA (guselkumab), a First-in-Class Treatment for Active Psoriatic Arthritis (PsA)

Original Title:Johnson & Johnson’s “First-in-Class” TREMFYA Approved by EU for Active Psoriatic Arthritis