New First-in-Class Phase 3 TREMFYA® (guselkumab) Data Demonstrate Sustained Improvement in Psoriatic Arthritis Joint and Skin Symptoms at Week 52

June 04, 2020 /Bio ValleyBIOON/ -- Janssen Pharmaceuticals, a subsidiary of Johnson & Johnson (JNJ), recently at the 2020 European Alliance of Associations for Rheumatology (EULAR) electronicMeetingNew data from two Phase III clinical studies (DISCOVER-1 and DISCOVER-2) were announced. These two studies evaluated the efficacy and safety of Tremfya® (tremfya®, generic name: guselkumab) in adult patients with active psoriatic arthritis (PsA). The new data showed that at Week 52, Tremfya demonstrated improvements across multiple clinical outcomes, including joint symptoms, skin symptoms, soft tissue inflammation, physical function, and reduction in radiographic progression.

Tremfya is a monoclonal antibody that selectively binds to the p19 subunit of interleukin-23 (IL-23) and inhibits its interaction with the IL-23 receptor. IL-23 is a key driver in the pathogenesis of inflammatory diseases such as psoriasis and psoriatic arthritis (PsA).

Notably, the newly released data represent the first one-year Phase III results evaluating a p19 subunit-specific IL-23 inhibitor in active psoriatic arthritis (PsA). Currently, Tremfya has not been approved for the treatment of PsA. Based on the primary endpoint results from the aforementioned two studies, Janssen submitted an application to the U.S. Food and Drug Administration (FDA) in September 2019.FDA) submitted a supplemental Biologics License Application (sBLA) for Tremfya for the treatment of adult patients with active Psoriatic Arthritis (PsA).

Principal Investigator of the DISCOVER-1 Study, University of Rochester Medical Center ClinicalImmunologyDr. Christopher Ritchlin, Director of the Research Center and Chief of the Division of Allergy & Immunology and Rheumatology, stated, “Patients with active psoriatic arthritis (PsA) face debilitating symptoms and inflammation that can ultimately lead to irreversible joint damage. The findings from the DISCOVER-1 and DISCOVER-2 studies are highly encouraging for both patients and physicians who may be seeking new treatment options with a mechanism of action distinct from TNFα biologics to address the multifaceted spectrum of PsA symptoms.”

The DISCOVER-1 and DISCOVER-2 studies evaluated the efficacy and safety of Tremfya versus placebo. The DISCOVER-1 study included patients who were biologic-naïve (had not previously received biologic therapy) or had received anti-Tumorpatients treated with tumor necrosis factor-alpha (TNF-α) biologics. The DISCOVER-2 study included only biologic-naïve patients and also assessed radiographic progression of joint damage. In both studies, patients were randomized to receive Tremfya 100 mg every 4 weeks (Q4W) or every 8 weeks (Q8W) for 52 weeks; patients receiving placebo switched to Tremfya Q4W at Week 24 and continued treatment through Week 52.

The 24-week results of two studies were published in April this year in The Lancet, a top-tier international medical journal. The results showed that both studies met their primary endpoints: after 24 weeks of treatment, a significantly higher proportion of patients in the Tremfya group achieved at least a 20% improvement in disease signs and symptoms (ACR20 response) compared to the placebo group. Furthermore, compared with the placebo group, the Tremfya group demonstrated significant improvements across multiple secondary endpoints, including joint symptoms, skin symptoms, soft tissue inflammation and disease activity, physical function, and health-related quality of life.

Psoriatic Arthritis (Image source: onhealth.com)

In these two studies, the American College of Rheumatology (ACR) remission rates at Week 52 included non-responder imputation (NRI) data, which classified patients who discontinued the study from Week 24 to Week 52 as non-responders.

—Week 52 data from the DISCOVER-1 study showed:(1) In the Tremfya Q4W and Q8W groups, 73% and 60% of patients, respectively, achieved ACR20 response, and 54% and 39% of patients, respectively, achieved ACR50 response (NRI). (2) Among patients with clinically relevant psoriasis at baseline, 83%, 69%, and 82% of patients in the Tremfya Q4W group, the Q8W group, and the group switched from placebo to Q4W, respectively, achieved an IGA score of 0 (complete clearance of skin lesions) or 1 (almost complete clearance of skin lesions) with at least a 2-grade improvement from baseline (observed data).

—Data from Week 52 of the DISCOVER-2 study showed:(1) In the Tremfya Q4W and Q8W groups, 71% and 75% of patients, respectively, achieved an ACR20 response, and 46% and 48% of patients, respectively, achieved an ACR50 response (NRI). (2) Among patients with clinically relevant psoriasis at baseline, 84%, 77%, and 84% of patients in the Tremfya Q4W group, the Q8W group, and the group switching from placebo to Q4W, respectively, achieved an IGA score of 0 (complete clearance of skin lesions) or 1 (almost complete clearance of skin lesions), with an improvement of at least 2 grades from baseline (observed data). (3)During the 52-week treatment period, Tremfya Q4W and Q8W demonstrated sustained improvement in inhibiting radiographic progression of joint structural damage (observed data).

—Other findings from two studies:Week 52 showed improvement compared with Week 24 in multiple secondary endpoints, including: ACR70 response, complete resolution of soft tissue inflammation (enthesitis and dactylitis), Disease Activity Score (DAS-28), C-reactive protein (CRP), Minimal Disease Activity (MDA), Very Low Disease Activity (VLDA), improvement in physical function (Health Assessment Questionnaire Disability Index [HAQ-DI]), and general health outcomes (SF-36 Physical Component Summary [PCS] and Mental Component Summary [MCS]).

In the two studies, Tremfya demonstrated good tolerability, and the observed adverse events (AEs) were generally consistent with those reported in previous studies of Tremfya and with current prescribing information.

Alyssa Johnsen, Ph.D., Vice President of Janssen Research & Development and Head of the Rheumatology Therapeutic Area, stated, “The efficacy of Tremfya in the treatment of PsA was demonstrated to be superior to placebo through Week 24. These new data show that efficacy is maintained through Week 52, and the safety profile is consistent with the established safety profile of Tremfya in patients with psoriasis.”

Tremfya is a human monoclonal antibody against the p19 subunit of interleukin-23 (IL-23), and it is the first approved selective IL-23 inhibitor. IL-23 is a cytokine involved in variousAutoimmunityplayed a key role in inflammatory diseases. Currently, Tremfya is also being developed for otherAutoimmunityTreatment of inflammatory diseases, including Crohn's disease (Phase IIb/III), ulcerative colitis (Phase IIb/III), and hidradenitis suppurativa (Phase II). Tremfya is administered via subcutaneous injection. The dosing regimen for the treatment of plaque psoriasis is 100 mg administered at Weeks 0 and 4, followed by 100 mg every 8 weeks thereafter.

To date, Tremfya has been approved in multiple countries and regions worldwide for the treatment of adult patients with moderate to severe plaque psoriasis. In China, Tremfya (Tremfya) was approved for marketing in Hong Kong in November 2018; it was submitted for approval in mainland China in late June 2019 and received approval from the National Medical Products Administration (NMPA) of China in December 2019 for the treatment of adult patients with moderate to severe plaque psoriasis who are candidates for systemic therapy.

Notably, Tremfya was included in the “First Batch of Overseas New Drugs Urgently Needed for Clinical Use” released by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA), with therapeutic indications covering erythrodermic psoriasis, plaque psoriasis, pustular psoriasis, psoriatic arthritis, and psoriasis vulgaris. The NMPA expedited the approval of Tremfya’s market launch through the priority review and approval pathway. (Bioon.com)

Original Source: New First-in-Class Phase 3 TREMFYA® (guselkumab) Data Demonstrate Improvement in Psoriatic Arthritis Joint and Skin Symptoms at Week 52