New Phase 3b Psoriatic Arthritis (PsA) Data Show TREMFYA® ▼ (guselkumab) Achieved Sustained Improvement in Joint Symptoms and Rate of Complete Skin Clearance in Patients with Inadequate Response to Tumour Necrosis Factor Inhibition (TNFi-IR)

New Phase 3b Psoriatic Arthritis (PsA) Data Show TREMFYA^® ▼ (guselkumab) Achieved Sustained Improvement in Joint Symptoms and Rate of Complete Skin Clearance in Patients with Inadequate Response to Tumour Necrosis Factor Inhibition (TNFi-IR)

 

44.4 percent achieved ≥20 percent improvement in joint symptoms (ACR20) at week 24 (57.7 percent at week 48) and 30.8 percent achieved complete skin clearance (PASI 100) at week 24 (53.4 percent at week 48) in COSMOS, the first study of a selective interleukin (IL)-23 inhibitor in a true TNFi-IR patient population

 

High Wycombe, UK,  June 4, 2021 – The Janssen Pharmaceutical Companies of Johnson & Johnson announced new efficacy and safety data for 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 tumour necrosis factor inhibition (TNFi).[i]

In the COSMOS Phase 3b study, significantly higher proportions of patients treated with guselkumab showed joint symptom improvement and complete skin clearance versus placebo at week 24 in this true TNFi-IR^a patient population, which is often more difficult to treat.1^,[ii] 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 guselkumab, a first-in-class selective IL-23 inhibitor therapy approved in the EU to treat adults with moderate to severe plaque psoriasis (PsO) who are candidates for systemic therapy, as well as adults with active PsA who have had an inadequate response (IR) or who have been intolerant to a prior disease-modifying antirheumatic drug (DMARD) therapy.[iii]

PsA is a chronic, progressive, immune-mediated disease characterised by pain, stiffness, and swelling in and around both peripheral and axial joints as well as itch and discomfort from skin lesions.[iv] People living with PsA can also suffer from sleep disorders, fatigue, stress, and depression.[v],[vi],[vii] 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.[viii],[ix]

“The diverse manifestations, varying natural history, and potential severity of PsA mean that delivering treatments that are generally well-tolerated 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 guselkumab 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:

• Joint Symptom Improvement: 44.4 percent of patients who received guselkumab 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.1 ACR20 response rates increased at one year (57.7 percent of guselkumab patients at week 48 utilising non-responder imputation [NRI]; with this method of analysis, patients with missing data were considered non-responders).1 Guselkumab 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 Physical Component Summary [PCS] score).1^,e 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).1
• Complete Skin Clearance Rate: At week 24, the proportion of patients with ≥3 percent body surface area psoriatic involvement and an Investigator's Global Assessment (IGA)^g score of ≥2 at baseline achieving complete skin clearance (100 percent improvement in Psoriasis Area Severity Index [PASI])^h was significantly higher among those receiving guselkumab than those receiving placebo (30.8 percent vs 3.8 percent, p<0.001).¹ At one year (week 48), PASI 100 response rates increased to 53.4 percent of patients receiving guselkumab (utilising NRI).1
• Safety Profile: Guselkumab demonstrated a consistent safety profile with low rates of adverse events (AEs) leading to discontinuation and serious AEs (SAEs).¹ Through week 56, for patients randomised to guselkumab who received at least one administration of drug, there were 149.3 AEs, 6.2 SAEs, and 3.6 AEs leading to treatment discontinuation per 100 patient years. Moreover, there were 39.7 infections and 0.5 serious infections per 100 patient years.1

“These results further our understanding of the efficacy of guselkumab 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 wellbeing. We are committed to continuing our research in PsA in order to advance therapeutic options that may help more patients reach their treatment goals.”

Later this year, Janssen will treat 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 guselkumab on the inhibition of radiographic progression of joint structural damage in patients with active PsA.[x]

Abstracts can be accessed on the EULAR 2021 website at: http://scientific.sparx-ip.net/archiveeular

Footnotes:

1. Inadequate Response to Tumour Necrosis Factor Inhibition (TNFi-IR) was defined by the presence of active PsA despite previous treatment with either one or two anti-TNF alpha agents or a lack of benefit of an anti-TNF alpha therapy. This was documented in the participant history by the treating physician, after at least 12 weeks of etanercept, adalimumab, golimumab, or certolizumab pegol therapy (or biosimilars) and/or at least a 14-week dosage regimen (i.e., at least four doses) of infliximab (or biosimilars).[xi]
2. Dr Gossec is a paid consultant for Janssen. She has not been compensated for any media work.
3. ACR20/50/70 response is defined as both at least 20/50/70 percent improvement from baseline in the number of tender and swollen joints, and at least 20/50/70 percent improvement from baseline in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure (HAQ-DI), visual analogue pain scale, and erythrocyte sedimentation rate or C-reactive protein.[xii]
4. HAQ-DI is a patient questionnaire that assesses physical function and disability across rheumatic diseases.[xiii]
5. SF-36 is a set of generic, coherent, and easily administered quality-of-life measures that rely upon patient self-reporting.[xiv]
6. LEI is an assessment of periarticular soft tissue tenderness in patients,[xv] and DSS is a composite assessment that measures tenderness and digit circumference.[xvi]
7. IGA Score is a five-point scoring system used to characterise PsO severity. Score range from 0 to 5 and represent cleared (0), minimal/almost (1), mild (2), moderate (3), severe (4). IGA PsO response was defined as an IGA score of 0 (cleared) or 1 (minimal) with a ≥2 reduction in IGA score from baseline.[xvii]
8. PASI 75/90/100 responses are defined as at least 75/90/100 percent improvement in the PASI score from baseline. The PASI score grades the amount of surface area covered by PsO plaques in each body region, and the degree of plaque redness, thickness, and scaliness.[xviii]

More About Psoriatic Arthritis

PsA is a chronic, immune-mediated inflammatory disease characterised by peripheral joint inflammation, enthesitis (pain where the bone, tendon and ligament meet), dactylitis (severe inflammation of the finger and toe joints), axial disease, and the skin lesions associated with PsO.4^,5,[xix]^,[xx]  In addition, in patients with PsA, comorbidities such as obesity, cardiovascular diseases, anxiety and depression are often present.5^,6 Studies show up to 30 percent of people with PsO also develop PsA.5^,[xxi] 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 time.5 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.[xxii]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.4

 

About COSMOS (NCT03796858; EudraCT 2018-003214-41)10^,[xxiii]

COSMOS was a Phase 3b, multicentre, randomised, double-blind, placebo-controlled clinical trial to evaluate the safety and efficacy of guselkumab in 285 patients with active PsA and an IR to TNFi therapy. The primary endpoint was ACR20 response at week 24. Participants were randomised (2:1) to receive guselkumab 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 guselkumab, compared with placebo and a 32-week active-treatment and safety follow-up period for additional analysis of the efficacy and safety of guselkumab. Through week 48, 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 TREMFYA^® (guselkumab)

Developed by Janssen, guselkumab is a fully human monoclonal antibody that selectively binds to the p19 subunit of IL-23 and inhibits its interaction with the IL-23 receptor.3 Guselkumab is approved as a prescription medicine in the UK for the treatment of adult patients with moderate to severe plaque PsO who are candidates for injections or pills (systemic therapy). It also has approved indications in PsO in the EU, US, Canada, Japan and a number of other countries worldwide for the treatment of adult patients with moderate to severe plaque PsO who may benefit from systemic therapy, or phototherapy (treatment using ultraviolet [UV] light).3

 

Guselkumab was approved by the European Commission in November 2020 for adults with active PsA who have had an inadequate response or been intolerant to a prior disease-modifying antirheumatic drug (DMARD) therapy. Guselkumab is also approved for PsA in the US, Canada, Japan, Brazil, Ecuador, and Taiwan. The PsA approval was based on results from DISCOVER-1 and DISCOVER-2, which showed guselkumab reached each study’s primary endpoint of ACR20 response at 24 weeks. Complete study results were previously published in The Lancet.[xxiv],[xxv]

 

IL-23 is an important driver of the progression of inflammatory immune-mediated diseases such as psoriasis and PsA.[xxvi] In the UK, guselkumab is administered as a 100 mg SC injection once every 8 weeks, after starter doses at weeks 0 and 4 for both plaque psoriasis and PsA, with 100 mg SC doses every 4 weeks considered in patients with PsA who are at high risk for joint damage according to clinical judgement.3

 

The Janssen Pharmaceutical Companies of Johnson & Johnson maintain exclusive worldwide marketing rights to TREMFYA^®.

 

Important Safety Information

Very common (≥10%) and common AEs (≥1%) in controlled periods of clinical studies with guselkumab were respiratory tract infections, increased transaminases, headache, diarrhoea, arthralgia and injection site reactions.3 Uncommon AEs (≥0.1%) observed were herpes simplex infections, tinea infections, gastroenteritis, decreased neutrophil count, hypersensitivity, anaphylaxis, urticaria and rash. Most were considered to be mild and did not necessitate discontinuation of study treatment.3

 

In PsA clinical studies, an increased incidence of liver enzyme elevations was observed in patients treated with guselkumab q4w compared to patients treated with guselkumab q8w or placebo.3

 

When prescribing guselkumab q4w in PsA, it is recommended to evaluate liver enzymes at baseline and thereafter according to routine patient management. If increases in ALT or AST are observed and drug-induced liver injury is suspected, guselkumab should be temporarily interrupted until this diagnosis is excluded.3

 

Please refer to the full Summary of Product Characteristics for full prescribing information for guselkumab: https://www.medicines.org.uk/emc/product/9587/smpc.

 

▼ AEs should be reported. This medicinal product is subject to additional monitoring and it is therefore important to report any suspected AEs related to this medicinal product. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. AEs should also be reported to Janssen-Cilag Ltd on 01494 567447 or via email at DSafety@its.jnj.com.

 

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/uk.

Follow us at www.twitter.com/JanssenUK.

 

Janssen-Cilag International NV, the marketing authorisation holder for TREMFYA^® in the EU, Janssen-Cilag Limited and Janssen Research & Development, LLC, are 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 ongoing and planned development efforts involving TREMFYA^® (guselkumab) as a treatment for adult patients with active psoriatic arthritis. 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 behaviour 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

 

 

 

 

 

 

 

[i] Coates L, et al. Efficacy and Safety of Guselkumab in Patients with Active Psoriatic Arthritis Who Demonstrated Inadequate Response to Tumor Necrosis Factor Inhibition: Week 24 Results of a Phase 3b, Randomized, Controlled Study. Presented at EULAR Virtual Congress June 2-5, 2021. OP0230.

[ii] Ogdie A and Coates L. The Changing Face of Clinical Trials in Psoriatic Arthritis. Curr Rheumatol Rep 2017;19(4):21.

[iii] European Medicines Agency. TREMFYA Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/tremfya-epar-product-information_en.pdf. Accessed June 2021.

[iv] Belasco J and Wei N. Psoriatic Arthritis: What is Happening at the Joint? Rheumatol Ther 2019;6(3):305-315.

[v] National Psoriasis Foundation. About Psoriatic Arthritis. Available at: https://www.psoriasis.org/about-psoriatic-arthritis/. Accessed June 2021.

[vi] Haddad A and Zisman D. Comorbidities in Patients with Psoriatic Arthritis. Rambam Maimonides Med J 2017;8(1):e0004.

[vii] Husni ME et al. Seminars in Arthritis and Rheumatism 2017;47(3):351-360.

[viii] Curtis J, et al. Guselkumab Provides Sustained Improvements in Work Productivity and Non-work Activity in Patients With Psoriatic Arthritis: Results Through 1 Year of a Phase 3 Trial. Presented at EULAR Virtual Congress June 2-5, 2021. POS1026.

[ix] Curtis J, et al. Clinical Characteristics & Outcomes Associate With Work Productivity in Bio-naïve Patients With Active Psoriatic Arthritis Through Week 24 of the DISCOVER-2 Study. Presented at EULAR Virtual Congress June 2-5, 2021. POS0200.

[x] Clinicaltrials.gov. A Study of Guselkumab in Participants With Active Psoriatic Arthritis (APEX). Identifier NCT04882098. Available at: https://clinicaltrials.gov/ct2/show/NCT04882098. Accessed June 2021.

[xi] Clinicaltrials.gov. A Study of Guselkumab in Participants With Active Psoriatic Arthritis and an Inadequate Response to Anti-Tumor Necrosis Factor Alpha (Anti-TNF Alpha) Therapy (COSMOS). Identifier NCT03796858. Available at: https://clinicaltrials.gov/ct2/show/NCT03796858. Accessed June 2021.

[xii] Felson D and LaValley M. The ACR20 and Defining a Threshold for Response in Rheumatic Diseases: Too Much of a Good Thing. Arthritis Res Ther 2014;16(1),101.

[xiii] Bruce B and Fries J. The Stanford Health Assessment Questionnaire: Dimensions and Practical Applications. Health Qual Life Outcomes 2003;1(1),20.

[xiv] RAND Corporation. 36-Item Short Form Survey (SF-36). Available at: https://www.rand.org/health-care/surveys_tools/mos/36-item-short-form.html. Accessed June 2021.

[xv] Ferguson E and Coates L. Optimisation of Rheumatology Indices: Dactylitis and Enthesitis in Psoriatic Arthritis. Clin Exp Rheumatol 2014;32(Suppl 85):s113-117.

[xvi] Helliwell P, et al. Development of an Assessment Tool For Dactylitis in Patients With Psoriatic Arthritis. The Journal of Rheumatology 2005;32(9),1745-1750.

[xvii] Langley R, et al. The 5-Point Investigator’s Global Assessment (IGA) Scale: A Modified Tool For Evaluating Plaque Psoriasis Severity in Clinical Trials. J Dermatol Treat 2015;26(1):23-31.

[xviii] Bożek A and Reich A. The Reliability of Three Psoriasis Assessment Tools: Psoriasis Area And Severity Index, Body Surface Area and Physician Global Assessment. Adv Clin Exp Med 2017;26(5):851-6.

[xix] Creaky Joints. What is Enthesitis? Available at: https://creakyjoints.org/symptoms/what-is-enthesitis/. Accessed June 2021.

[xx] Creaky Joints. What is Dactylitis? Available at: https://creakyjoints.org/symptoms/what-is-dactylitis/. Accessed June 2021.

[xxi] Ogdie A and Weiss P. The Epidemiology Psoriatic Arthritis. Rheum Dis Clin North Am 2015;41(4):545–568.

[xxii] Husted JA, et al. Occurrence and Correlates of Fatigue in Psoriatic arthritis. Ann Rheum Dis 2008;68(10):1553–1558.

[xxiii] Clinicaltrialsregister.eu. Phase 3b, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Guselkumab Administered Subcutaneously in Participants with Active Psoriatic Arthritis and an Inadequate Response to Anti-Tumor Necrosis Factor Alpha (Anti-TNFα) Therapy (COSMOS). Identifier: 2018-003214-41. Available at: https://www.clinicaltrialsregister.eu/ctr-search/trial/2018-003214-41/BE. Accessed June 2021.

[xxiv] Deodhar A, et al. Guselkumab in patients with active psoriatic arthritis who were biologic-naive or had previously received TNFα inhibitor treatment (DISCOVER-1): a double-blind, randomised, placebo-controlled phase 3 trial. The Lancet 2020;395(10230):1115-1125.

[xxv] Mease P, et al. Guselkumab in biologic-naive patients with active psoriatic arthritis (DISCOVER-2): a double-blind, randomised, placebo-controlled phase 3 trial. The Lancet 2020; 395(10230): 1126-1136.

[xxvi] Benson J.M., et al. Discovery and Mechanism of Ustekinumab. MAbs 2011;3(6):535-545.