SPRING HOUSE, PENNSYLVANIA, January 24, 2022 – The Janssen Pharmaceutical Companies of Johnson & Johnson today announced a Network Meta-Analysis (NMA) comparing first-in-class interleukin (IL)-23 inhibitor TREMFYA® (guselkumab) to all advanced therapiesa approved for active psoriatic arthritis (PsA) using data from 33 Phase 3 randomized clinical trials (RCTs).1 The NMA concluded TREMFYA ranked highestb for skin clearance based on Psoriasis (PsO) Area Severity Index (PASI)c 90 response among 23 treatment regimens (15 unique treatments including IL-23 inhibitors like TREMFYA and risankizumab, subcutaneous [SC] tumor necrosis factor inhibitors [TNFi], and Janus kinase inhibitors [JAKi]).1 In terms of joint inflammation improvement, both TREMFYA dosing regimens (100 mg every four weeks [q4w] and every eight weeks [q8w])d were comparableb to most other treatments for the modified van der Heijde-Sharp (vdH-S)e score, and TREMFYA was generally comparableb to TNFi and most IL-17Ai for American College of Rheumatology (ACR) 20 response.1,f The analysis also confirmed the established safety profile of TREMFYA in active PsA.1 The NMA is being presented at the Maui Dermatology 2022 Meeting taking place January 24-28, 2022. TREMFYA is U.S. Food and Drug Administration (FDA) approved for administration as a 100 mg SC injection q8w, following two initial doses at weeks 0 and 4.2,d
“This comprehensive analytical approach helps to provide a useful comparative picture of available psoriatic arthritis medicines,” said Philip J. Mease,g M.D., Swedish Medical Center/Providence St. Joseph Health and University of Washington in Seattle, Washington. “In my experience, thorough NMAs such as this one can help equip physicians to discuss treatment choices and therapeutic outcomes with their patients in daily practice.”
NMA is a structured, protocol-driven analytical process widely accepted and utilized by regulatory agencies, health technology assessment agencies and medical guideline committees to comparatively evaluate treatment options where head-to-head data are limited or unavailable.3-5 NMA is the most cited and the most comprehensive method available to compare studies indirectly; however, NMAs cannot replace and should not be considered the same as head-to-head clinical trials. In this NMA, the timing of primary endpoint assessment varied across RCTs, and placebo was used as the reference treatment throughout with the exception of two head-to-head studies.1 Baseline risk adjustment was used to account for heterogeneity across study populations. The NMA builds on previous analyses, including a 2021 publication in Rheumatology, and now incorporates all recent clinical data updates, including the COSMOS study of TREMFYA in PsA patients who had an inadequate response to TNFi, as well as data for two new comparators, the IL-23i risankizumab and the JAKi upadacitinib.1,6,7
NMA results showed:1
· Skin Clearance: TREMFYA ranked first and secondb in PASI 90 response for q4wd and q8w dosing, respectively.
· Joint Inflammation Improvement: TREMFYA was comparable to SC TNFi and most IL-17Ai, as measured by ACR20 response. While dosing frequency impacted modified vdH-S score,e both TREMFYA dosing regimens achieved improvements that were comparable to most treatments and both doses of TREMFYA ranked more highly on vdH-S score than risankizumab and upadacitinib.b
· Low Numbers of Serious Adverse Events (SAEs): TREMFYA showed low rates of SAEs, with both dosing regimens ranking favorably among the 23 treatments for low rates of events. The number of SAEs for TREMFYA were consistent with the established TREMFYA safety profile.1
“Psoriatic arthritis is a complex disease, and physicians must consider many factors when making treatment decisions, including the relative efficacy of therapies in treating both skin and joints, as well as established safety,” said Terence Rooney, M.D., Vice President, Rheumatology and Maternal-Fetal Immunology Disease Area Leader, Janssen Research & Development, LLC. “NMAs are a comprehensive, well-established approach, and can provide physicians with useful information on available therapies.”
TREMFYA was approved in the U.S. for the treatment of adult patients with moderate to severe plaque PsO in July 2017 and in July 2020 for adults with active PsA.2 The PsA approval was based on results from DISCOVER-1 and DISCOVER-2, which showed TREMFYA achieved the studies’ primary endpoint of ACR20 response at 24 weeks.8,9 A comprehensive analysis of DISCOVER-2 data was recently published in Arthritis & Rheumatology, representing the final results of the first-ever two-year clinical trial with an open label extension investigating a selective IL-23 inhibitor therapy in active PsA.10
Janssen will present five additional posters at the Maui Dermatology Meeting, including the study design of APEX (NCT04882098),11 investigating the effect of TREMFYA on radiographic progression;h the design of the SOLSTICE trial (NCT04936308),12 which further evaluates TREMFYA efficacy for PsA patients with intolerance or inadequate response to TNF therapy; evidence of molecular and genetic distinctions between patients with axial PsA (axPsA) and ankylosing spondylitis and the significant pharmacodynamic effects of TREMFYA in axPsA patients; and real-world evidence for PsA patients initiating TREMFYA treatment in the CorEvitas Psoriatic Arthritis/Spondyloarthritis (PsA/SpA) Registry.
Editor’s Note:
a. Advanced therapies were defined as any targeted or biologic therapies for the treatment of PsA including: TNFi, JAKi, IL-17Ai, IL-12/23i, IL-23i, PDE4i, CTLA-4i, biologic biosimilar agents, and placebo/no treatment.1
b. Results are summarized by ranking treatments according to findings derived from NMAs. Conclusions (i.e., comparable) are based on an overlap of pairwise 95 percent credible intervals.1
c. PASI 90 is defined as at least 90 percent improvement from baseline in the PASI score. The PASI score grades the amount of surface area on each body region that is covered by PsO plaques and the severity of plaques for their redness, thickness, and scaliness.13 PASI 90 was not a controlled endpoint in DISCOVER-1 or -2.8,9
d. TREMFYA q4w dosing is not currently FDA-approved.2
e. The PsA-modified vdH-S score combines erosion and joint space narrowing scores derived from radiographs of joints in body regions impacted by PsA.14 TREMFYA is not approved in the U.S. for inhibition of structural damage.2
f. ACR20 response is defined as both at least 20 percent improvement from baseline in the number of tender and number of swollen joints, and a 20 percent improvement from baseline in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure, visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein.15
g. Dr. Mease is a paid consultant for Janssen. He has not been compensated for any media work.
h. Radiographic progression is a key indicator of structural damage, which includes erosion and joint space narrowing. Radiographic progression is not in the FDA label for TREMFYA.2
About the Network Meta-Analysis1
A systematic literature review was conducted to identify randomized controlled trials up to February 2021. A hand search identified newer agents up to July 2021. These searches identified 33 Phase 3 RCTs studying 15 targeted therapies for PsA approved or under review by the U.S. FDA or the European Medicines Agency in patients who were TNFi-naïve, TNFi-experienced, had an inadequate response (IR), or mixed populations for inclusion in this NMA, through July 2021. Bayesian NMAs were performed to compare therapies on ACR20 response, PASI response, modified vdH-S score and SAEs. Analyses used random effects models wherever possible, and fixed effects models when not. Wherever possible, analyses included meta-regression on baseline risk (placebo response) in order to reduce bias. Multinomial models were used for ACR and PASI. Several NMAs have compared the efficacy of treatments available for PsA, but none of these analyses have included the latest Phase 3 data for TREMFYA in the TNFi-IR population or the latest comparators risankizumab and upadacitinib.16-19 The objective of this study was to update the prior NMAs to include these new data to determine the relative skin and joint efficacy and safety for therapies available for PsA through NMA.
This NMA adheres to all governing standards and requirements as demanded by global health technology assessment agencies, journal review committees and regulatory authorities. The NMA was funded by Janssen Research & Development, LLC.
About COSMOS (NCT03796858)7
COSMOS was a Phase 3b, multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of TREMFYA in 285 patients with active PsA and IR to TNFi therapy. The primary endpoint was ACR20 response at week 24. Participants were randomized (2:1) to receive TREMFYA 100 mg at weeks 0, 4 and q8w thereafter, or placebo. The study included two periods: a 24-week double-blind, placebo-controlled period for the primary analysis of the efficacy and safety of TREMFYA compared with placebo and a 32-week active-treatment and safety follow-up period for additional analysis of the efficacy and safety of TREMFYA. Through week 48, non-responder imputation (NRI) rules were used for missing data (after the application of treatment failure rules [TFR]). Safety was monitored throughout the study to week 56.
About DISCOVER-1 (NCT03162796)8
DISCOVER-1 was a randomized, double-blind, multicenter Phase 3 study evaluating the efficacy and safety of TREMFYA administered by SC injection in participants with active PsA, including those previously treated with one or two TNF inhibitors. DISCOVER-1 evaluated 381 participants who were treated and followed through approximately one year. The primary endpoint was response of ACR20 at week 24 and primary endpoint data were previously presented at scientific congresses and published in The Lancet. In addition to ACR20, multiple other clinical outcomes were assessed, including ACR50/70, resolution of soft tissue inflammation, enthesitis and dactylitis, improvement in physical function, skin clearance (IGA), and general health outcomes (36-Item Short-Form Health Survey [SF-36] Physical Component Summary [PCS] and Mental Component Summary [MCS]).
The study consisted of a screening phase of up to six weeks, a blinded treatment phase of 52 weeks that included a placebo-controlled period from week 0 to week 24 and a blinded active treatment period from week 24 to week 52. It also included a safety follow-up phase through week 60 (i.e., approximately 12 weeks from the last administration of study agent at week 48). Efficacy, safety, pharmacokinetic, immunogenicity and biomarker evaluations were performed in the study on a defined schedule.
About DISCOVER-2 (NCT03158285)9
DISCOVER-2 is a randomized, double-blind, multicenter Phase 3 study evaluating the efficacy and safety of TREMFYA administered by SC injection in biologic-naïve patients with active PsA. DISCOVER-2 evaluated 739 participants who were treated and followed through approximately two years. The primary endpoint was response of ACR20 at week 24 and primary endpoint data were previously presented at scientific congresses and published in The Lancet. In addition to ACR20, multiple other clinical outcomes were assessed, including ACR50/70; resolution of soft tissue inflammation, enthesitis and dactylitis; improvement in physical function; skin clearance (IGA); and general health outcomes (SF-36 PCS and MCS). DISCOVER-2 also assessed changes in structural damage as a key secondary endpoint (PsA-modified vdH-S score).
The study consisted of a screening phase of up to six weeks, a blinded treatment phase of approximately 100 weeks that included a placebo-controlled period from week 0 to week 24 and a blinded active treatment period from week 24 to week 100. It also included a safety follow-up phase through week 112 (i.e., approximately 12 weeks after the last administration of study agent at week 100). Clinical efficacy, radiographic efficacy, health economics, safety, pharmacokinetics, immunogenicity, biomarker, and pharmacogenomics evaluations were performed in the study on a defined schedule.
About Psoriatic Arthritis (PsA)
PsA is a chronic, immune-mediated inflammatory disease characterized by peripheral joint inflammation, enthesitis (pain where the bone, tendon and ligament meet), dactylitis (severe inflammation of the fingers and toes), axial disease, and the skin lesions associated with plaque PsO.20-22 In addition, in patients with PsA, comorbidities, such as obesity, cardiovascular diseases, anxiety and depression are often present.23 Studies show up to 30 percent of people with plaque PsO also develop PsA.24 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 age.24 Nearly half of patients with PsA experience moderate fatigue and about 30 percent suffer from severe fatigue as measured by the modified fatigue severity scale.25 Although the exact cause of PsA is unknown, genes, the immune system and environmental factors are all believed to play a role in disease onset.26
About TREMFYA® (guselkumab)2
Developed by Janssen, TREMFYA is the first approved fully human monoclonal antibody that selectively binds to the p19 subunit of IL-23 and inhibits its interaction with the IL-23 receptor. IL-23 is an important driver of the pathogenesis of inflammatory diseases such as moderate to severe plaque PsO and active PsA.27 TREMFYA is approved in the U.S., Canada, Japan, and a number of other countries worldwide for the treatment of adults with moderate to severe plaque PsO who are candidates for injections or pills (systemic therapy) or phototherapy (treatment using ultraviolet light), and for the treatment of adult patients with active PsA. It is also approved in the EU for the treatment of moderate to severe plaque PsO in adults who are candidates for systemic therapy and for the treatment of active PsA in adult patients who have had an inadequate response or who have been intolerant to a prior disease-modifying antirheumatic drug therapy.
The Janssen Pharmaceutical Companies of Johnson & Johnson maintain exclusive worldwide marketing rights to TREMFYA®.
IMPORTANT SAFETY INFORMATION
What is the most important information I should know about TREMFYA®?
TREMFYA® is a prescription medicine that may cause serious side effects, including:
Serious Allergic Reactions. Stop using TREMFYA® and get emergency medical help right away if you develop any of the following symptoms of a serious allergic reaction:
o fainting, dizziness, feeling lightheaded (low blood pressure)
o swelling of your face, eyelids, lips, mouth, tongue or throat
o trouble breathing or throat tightness
o chest tightness
o skin rash, hives
o itching
Infections. TREMFYA® may lower the ability of your immune system to fight infections and may increase your risk of infections. Your healthcare provider should check you for infections and tuberculosis (TB) before starting treatment with TREMFYA® and may treat you for TB before you begin treatment with TREMFYA® if you have a history of TB or have active TB. Your healthcare provider should watch you closely for signs and symptoms of TB during and after treatment with TREMFYA®.
Tell your healthcare provider right away if you have an infection or have symptoms of an infection, including:
o fever, sweats, or chills
o muscle aches
o weight loss
o cough
o warm, red, or painful skin or sores on your body different from your psoriasis
o diarrhea or stomach pain
o shortness of breath
o blood in your phlegm (mucus)
o burning when you urinate or urinating more often than normal
Do not take TREMFYA® if you have had a serious allergic reaction to guselkumab or any of the ingredients in TREMFYA®.
Before using TREMFYA®, tell your healthcare provider about all of your medical conditions, including if you:
· have any of the conditions or symptoms listed in the section “What is the most important information I should know about TREMFYA®?”
· have an infection that does not go away or that keeps coming back.
· have TB or have been in close contact with someone with TB.
· have recently received or are scheduled to receive an immunization (vaccine). You should avoid receiving live vaccines during treatment with TREMFYA®.
· are pregnant or plan to become pregnant. It is not known if TREMFYA® can harm your unborn baby.
· are breastfeeding or plan to breastfeed. It is not known if TREMFYA® passes into your breast milk.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
What are the possible side effects of TREMFYA®?
TREMFYA® may cause serious side effects. See “What is the most important information I should know about TREMFYA®?”
The most common side effects of TREMFYA® include: upper respiratory infections, headache, injection site reactions, joint pain (arthralgia), diarrhea, stomach flu (gastroenteritis), fungal skin infections, herpes simplex infections, and bronchitis.
These are not all the possible side effects of TREMFYA®. Call your doctor for medical advice about side effects.
Use TREMFYA® exactly as your healthcare provider tells you to use it.
Please read the full Prescribing Information, including Medication Guide for TREMFYA®, and discuss any questions that you have with your doctor.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.
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About the Janssen Pharmaceutical Companies of Johnson & Johnson
At Janssen, we’re creating a future where disease is a thing of the past. We’re the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity, and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Cardiovascular & Metabolism, Immunology, Infectious Diseases & Vaccines, Neuroscience, Oncology, and Pulmonary Hypertension.
Learn more at www.janssen.com. Follow us at www.twitter.com/JanssenGlobal.
Janssen Research & Development, LLC is a part of the Janssen Pharmaceutical Companies of Johnson & Johnson.
Cautions Concerning Forward-Looking Statements
This press release contains “forward-looking statements” as defined in the Private Securities Litigation Reform Act of 1995 regarding TREMFYA® (guselkumab) product development. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Research & Development, LLC, any of the other Janssen Pharmaceutical Companies and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson’s Annual Report on Form 10-K for the fiscal year ended January 3, 2021, including in the sections captioned “Cautionary Note Regarding Forward-Looking Statements” and “Item 1A. Risk Factors,” and in the company’s most recently filed Quarterly Report on Form 10-Q, and the company’s subsequent filings with the Securities and Exchange Commission. Copies of these filings are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. None of the Janssen Pharmaceutical Companies nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.
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References
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2. Food and Drug Administration. TREMFYA® Prescribing Information. Horsham, PA. 2017. Available at: https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/TREMFYA-pi.pdf. Accessed January 2022.
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16. Ruyssen-Witrand, A., et al. Efficacy and safety of biologics in psoriatic arthritis: a systematic literature review and network meta-analysis. RMD Open, 2020:6(1), e001117. https://doi.org/10.1136/rmdopen-2019-001117
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20. Belasco, J., & Wei, N. Psoriatic Arthritis: What is Happening at the Joint? Rheumatology and Therapy, 2019: 6(3), 305–315. https://doi.org/10.1007/s40744-019-0159-1
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22. Donvito T. CreakyJoints: What Is Dactylitis? The ‘Sausage Finger’ Swelling You Should Know About. Available at: https://creakyjoints.org/symptoms/what-is-dactylitis/. Accessed October 2021.
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