June 2, 2021: The Janssen Pharmaceutical Companies of Johnson & Johnson announced new efficacy and safety data for first-in-class TREMFYA® (guselkumab), including data from the first study evaluating a selective IL-23 inhibitor in adult patients with active PsA, all of whom had demonstrated inadequate response or intolerance to TNFi.
In the COSMOS Phase 3b study, significantly higher proportions of patients treated with TREMFYA showed joint symptom improvement and complete skin clearance versus placebo at week 24 in this true TNFi-IRa patient population, which is often more difficult to treat.1,2
These results are among the 34 scientific abstracts Janssen is presenting from the Company’s rheumatology portfolio at the EULAR E-Congress, many of which feature TREMFYA, the only selective IL-23 inhibitor therapy approved in the U.S. to treat both adults with moderate to severe plaque psoriasis (PsO) who are candidates for systemic therapy or phototherapy, as well as adults with active PsA.
PsA is a chronic, progressive, immune-mediated disease characterized by pain, stiffness, and swelling in and around both peripheral and axial joints as well as itch and discomfort from skin lesions.
People living with PsA can also suffer from sleep disorders, fatigue, stress, and depression.
Janssen data shared at EULAR show the severity of skin and joint symptoms of active PsA was significantly associated with a higher loss of work productivity and impact on daily activity outside of work.
“The diverse manifestations, varying natural history, and potential severity of PsA mean that delivering treatments that are safe and have long-term effectiveness is challenging. A number of patients do not reach treatment targets of remission or low inflammation with available therapies.
In particular, patients may either not respond well to TNFi, or respond but have a loss of response over time,” said study investigator Laure Gossec, M.D., Ph.D., Professor of Rheumatology in Pitie-Salpetriere Hospital and Pierre & Marie Curie University in Paris, France.b
“These COSMOS data reinforce TREMFYA as a therapeutic option with an alternative mechanism of action for adult patients with PsA when their disease management is complex because they have not responded to one or more therapies.”
COSMOS (Presentation #OP0230) results show:
Robust Joint Symptom Improvement: 44.4 percent of patients who received TREMFYA vs. 19.8 percent of patients who received placebo achieved at least 20 percent improvement in the American College of Rheumatology criteria (ACR20)c at week 24, the study’s primary endpoint.
ACR20 response rates increased at one year (57.7 percent of TREMFYA patients at week 48 utilizing non-responder imputation [NRI]; with this method of analysis, patients with missing data were considered non-responders).
TREMFYA was also superior to placebo in percentage of patients achieving ACR50 and improvement in physical function (Health Assessment Questionnaire Disability Index [HAQ-DI])d and general health outcomes (Short Form [SF]-36 and Physical Component Summary [PCS] scores).
Mean improvement in physical function increased at one year, with higher resolution rates of enthesitis and dactylitis seen as well (soft tissue inflammation measured by the Leeds Enthesitis Index [LEI]f and Dactylitis Severity Score [DSS], respectively).
Complete Skin Clearance: At week 24, the proportion of patients with ≥3 percent body surface area psoriatic involvement and an Investigator’s Global Assessment (IGA)g score ≥2 at baseline achieving complete skin clearance (100 percent improvement in Psoriasis Area Severity Index [PASI])h was significantly higher among those receiving TREMFYA than those receiving placebo (30.8 percent vs. 3.8 percent).
At one year (week 48), PASI 100 response rates increased to 53.4 percent of patients receiving TREMFYA (utilizing NRI).
TREMFYA efficacy and safety findings across additional abstracts (presentation numbers cited within) are also being presented:
Rapid and Durable Joint Symptom Improvement and Complete Skin Clearance:
In the DISCOVER-2 PsA trial, the robust response rates seen at week 24 for joint symptoms (ACR20/50/70), skin clearance (PASI 90/100), improved physical function (HAQ-DI), and enthesitis and dactylitis resolution persisted through two years, even when long-term response rates were conservatively estimated using NRI.
88 percent of patients who received TREMFYA (652/739) completed week 100 of the study, with low rates of radiographic progression of joint structural damage observed from week 52-100 (POS1027).
In DISCOVER-1 and -2, TREMFYA demonstrated meaningful improvements in individual components of the ACR criteria as early as week four.
At early study time points, both patients and physicians were able to discern improvements in signs and symptoms of arthritis that rapidly followed (within one assessment) reductions in systemic inflammation based on C-reactive protein levels (AB0525).
In a post-hoc analysis of pooled data from DISCOVER -1 and -2 patients with axial symptoms and imaging-confirmed sacroiliitis, TREMFYA resulted in numerically lower mean scores for all six Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)j components compared with placebo as early as week eight and through week 24, with mean scores maintained at week 52 using NRI (AB0524).
Established Safety Profile:
Pooled data from the active PsA trials, DISCOVER-1 and -2, and the PsO trials, VOYAGE 1 and 2, showed the TREMFYA safety profile was generally consistent between patients with PsA and PsO through one year.
Decreased neutrophil counts and elevations in hepatic transaminases – generally mild, transient and without sequalae – were somewhat more common in PsA than PsO patients (AB0528).
Through one year of follow-up with TREMFYA treatment in pooled DISCOVER-1 and -2 and VOYAGE 1 and 2 data, gastrointestinal-related serious adverse event (SAE) rates were low.
There were no reported cases of uveitis, opportunistic infections, or new onset/exacerbation of inflammatory bowel disease in TREMFYA-treated patients.
No new safety concerns were identified through one year (POS1031).
Physical, Social and Work Activity:
In an assessment of DISCOVER 2, observed mean T-scores showed improvement from baseline to week 24 in TREMFYA-treated patients vs. placebo across all seven domains of The Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29)k instrument: anxiety, depression, fatigue, pain interference, physical function, sleep disturbance, and social participation.
Maintenance of improvements in these health-reported outcomes was seen through week 52 (POS1029).
In patients with active PsA who were working at baseline, improvement in work productivity and non-work activity was greater with TREMFYA vs. placebo at week 24, and these improvements were sustained through week 52.
Improvements demonstrated may result in yearly indirect savings in costs associated with work productivity (POS1026).
“These results further our understanding of the efficacy of TREMFYA to treat the varied manifestations of PsA,” said Alyssa Johnsen, M.D., Ph.D., Vice President and Rheumatology Disease Area Leader, Janssen Research & Development, LLC.
“People with PsA live with joint, skin, and soft tissue symptoms, but also experience impacts on physical function and social and psychological well-being.
We are committed to continuing our research in PsA to advance therapeutic options that may help more patients reach their treatment goals.”
Later this year, Janssen will dose its first patient in the APEX (NCT04882098) study.
APEX is a newly initiated Phase 3b trial with long-term extension through three years to further assess the efficacy of TREMFYA on the inhibition of radiographic progression of joint structural damage in patients with active PsA.