Tremfya (Guselkumab) Demonstrates Sustained Skin and Joint Symptom Improvement in Active Psoriatic Arthritis Through Two Years: Phase 3 DISCOVER-2 Long-Term Data

March 16, 2021 News /BioValleyBIOON/ -- Janssen Pharmaceuticals, a subsidiary of Johnson & Johnson (JNJ), recently announced long-term data from the Phase III clinical trial (DISCOVER-2). This study evaluated the efficacy and safety of Tremfya (tremfya, generic name: guselkumab) in adult patients with active psoriatic arthritis (PsA). The data showed that the skin clearance, joint symptom relief, and safety observed at 24 weeks and one year (52 weeks) of Tremfya treatment were sustained over two years (Week 112). These findings also confirmed that the robust efficacy of Tremfya at Week 24 in terms of physical function, the physical aspects of health-related quality of life, and resolution of enthesitis and dactylitis persisted through Week 100. Furthermore, the study assessed radiographic progression after two years of treatment.

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 plaque psoriasis (PsO) and psoriatic arthritis (PsA).

It is worth mentioning that in the United States and the European Union,Tremfya is the first and only IL-23 inhibitor therapy approved for the treatment of adult patients with active psoriatic arthritis (PsA) and adult patients with moderate-to-severe plaque psoriasis (PsO).

The data released herein mark the first and only long-term Phase 3 study results for a selective IL-23 inhibitor in the treatment of psoriatic arthritis (PsA), including its impact on radiographic progression over up to two years. The data show that more than 50% of adult patients with active PsA achieved complete skin clearance (PASI 100), and 70% of patients achieved at least a 20% improvement in joint symptoms (ACR 20).

Philip J. Mease, MD, of the Swedish Medical Center/Providence St. Joseph Health and the University of Washington School of Medicine in Seattle, stated, “PsA is a chronic, painful, and debilitating disease, and many patients with PsA are still seeking lasting relief from their symptoms. These data indicate that the benefits observed with Tremfya in PsA were sustained over two years, which is positive news for both physicians and patients.”

Psoriatic Arthritis (Image source: onhealth.com)

The DISCOVER-2 study included only biologic-naïve patients and evaluated the efficacy and safety of Tremfya versus placebo, as well as radiographic progression of joint damage. In the study, patients were randomized to receive Tremfya 100 mg every 4 weeks (q4w) or every 8 weeks (q8w), while patients receiving placebo switched to Tremfya q4w at Week 24. Results showed that at Week 100:

—Complete clearance of skin lesions: Among patients with clinically meaningful skin involvement at baseline, 59% of those receiving Tremfya every 4 weeks (q4w) and 53% of those receiving Tremfya every 8 weeks (q8w) achieved complete clearance of skin lesions (Psoriasis Area and Severity Index [PASI] 100; using non-responder imputation [NRI], whereby subjects with missing data were assumed to be non-responders).

— Improvement in joint symptoms: Among randomized patients, 76% of those treated with Tremfya q4w and 74% of those treated with Tremfya q8w achieved at least a 20% improvement according to the American College of Rheumatology (ACR20) response criteria (using NRI).

—— Radiographic Progression: At Week 24, Tremfya q4w demonstrated a statistically significant inhibition of radiographic progression of joint structural damage (p=0.011; measured by the PsA-modified van der Heijde Sharp [vdH-S] score). Tremfya q8w showed a numerical inhibitory effect but was not statistically significant, with less radiographic progression compared to placebo (p=0.072). From Weeks 52 to 100, lower rates of radiographic progression of joint damage were observed in patients treated with Tremfya q4w (0.75) and Tremfya q8w (0.46); both treatment groups showed further numerical reductions compared to the results observed during Weeks 0–52 (1.06 for q4w; 0.99 for q8w). In patients who switched from placebo to Tremfya q4w at Week 24, the mean change in vdH-S score was 1.12 during the 0–24-week placebo period, 0.34 during Weeks 24–52 after initiating Tremfya q4w, and 0.13 during Weeks 52–100, indicating further numerical improvement in this group during the second year.

—Durability: Robust joint and skin response rates and mean improvements relative to baseline were maintained through Year 2. Among patients randomized to Tremfya q4w or q8w, approximately 90% continued Tremfya treatment through Week 100.

—Safety: In the safety analysis conducted at Week 112, no new safety signals were observed. The safety profile of Tremfya over 2 years of treatment in patients with active psoriatic arthritis (PsA) was consistent with that observed at 6 months and 1 year, and was largely comparable to the safety profile of Tremfya in patients with moderate-to-severe plaque psoriasis (PsO).。

Furthermore, the results showed that 56% of patients in the Tremfya q4w group and 55% of patients in the Tremfya q8w group achieved at least a 50% improvement in ACR score (using NRI). Among patients with clinically significant PsO at baseline, 62% of patients in the Tremfya q4w group and 55% of patients in the Tremfya q8w group achieved complete clearance of skin lesions, as assessed by an Investigator’s Global Assessment (IGA) score of 0 (using NRI).

Dr. Alyssa Johnsen, Vice President of Janssen Research & Development and Head of the Rheumatology Therapeutic Area, stated, “PsA is a chronic inflammatory disease affecting the skin, joints, and soft tissues; therefore, sustained control of this inflammation is important for both physicians and patients. These long-term study results further support our belief that Tremfya can significantly improve various manifestations of PsA over time.”

Tremfya is a human monoclonal antibody targeting 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 variousAutoimmunityhas played a pivotal role in the treatment of these diseases. To date, Tremfya has been approved in numerous countries and regions worldwide for the treatment of adult patients with moderate-to-severe plaque psoriasis (PsO) and adult patients with active psoriatic arthritis (PsA).

In China, Tremfya (Tenuoya) 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 List 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 accelerated the approval of Tremfya’s market launch through the priority review and approval pathway. (Bioon.com)

Original Source: New Phase 3 Data Show First-in-Class TREMFYA (guselkumab) Achieved Complete Skin Clearance and Favorable Joint Efficacy in Adult Patients with Active Psoriatic Arthritis (PsA) Through Two Years