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

SPRING HOUSE, Pa., June 3, 2020 /PRNewswire/ -- The Janssen Pharmaceutical Companies of Johnson & Johnson today announced new data from two Phase 3 clinical trials, DISCOVER-1 and DISCOVER-2, which showed that TREMFYA^® (guselkumab) demonstrated improvements in multiple clinical outcomes including joint symptoms, skin symptoms, soft tissue inflammation, physical function and reduction in radiographic progression at week 52 in adult patients with active psoriatic arthritis (PsA).^1,2 TREMFYA is currently not approved for the treatment of PsA in the U.S. Data from the two studies in the DISCOVER program formed the basis of the September 13, 2019 supplemental Biologics License Application submission to the U.S. Food and Drug Administration (FDA) for approval of TREMFYA and primary endpoint results were recently published in The Lancet.^3,4,5

"Those who are living with active psoriatic arthritis are faced with debilitating symptoms and inflammation which may ultimately lead to irreversible damage to the joints," said Christopher Ritchlinⁱ, M.D., M.P.H., Chief of the Division of Allergy, Immunology and Rheumatology and Director of the Clinical Immunology Research Center at the University of Rochester Medical Center in Rochester, New York and lead investigator of the DISCOVER-1 study. "Findings from the DISCOVER-1 and DISCOVER-2 studies are encouraging for patients and physicians alike who may be seeking new treatment options that utilize mechanisms of action different to anti-tumor necrosis factor (TNF) alpha biologics to combat the multi-faceted combination of symptoms presented by psoriatic arthritis."

DISCOVER-1 and DISCOVER-2 evaluated the efficacy and safety of TREMFYA compared to placebo. DISCOVER-1 included patients who were biologic-naïve or had previously been exposed to anti-TNF alpha biologics. DISCOVER-2 included patients who were biologic-naïve only; it also assessed radiographic progression of joint damage. In both studies, patients were randomized to TREMFYA 100 mg every 4 weeks (q4w) or every 8 weeks (q8w) for one year, or to placebo with crossover to TREMFYA q4w at week 24 through one year. These findings are being presented as poster tours (SAT0397/ SAT0402) at this year's European League Against Rheumatism (EULAR) E-Congress, at which Janssen is sharing data in a total of 32 abstracts.^1,2

In both studies, American College of Rheumatology (ACR) response rates at week 52 included non-responder imputation (NRI) data, which categorized patients who discontinued the study as non-responders from week 24 to 52.

In DISCOVER-1, data demonstrated that at week 52:¹

• 73 percent of TREMFYA q4w patients and 60 percent of TREMFYA q8w patients achieved ACR20; 54 percent of TREMFYA q4w patients and 39 percent of TREMFYA q8w patients achieved ACR50 (NRI).
• Among patients who had clinically relevant psoriasis at baseline, 83 percent of TREMFYA q4w patients, 69 percent of TREMFYA q8w patients and 82 percent of patients who crossed over from placebo to TREMFYA q4w achieved clear or almost clear skin with at least a 2 grade improvement from baseline as measured by the Investigator Global Assessment (IGA) score (observed data).⁶

In DISCOVER-2, data demonstrated that at week 52:² 

• 71 percent of TREMFYA q4w patients and 75 percent of TREMFYA q8w patients achieved ACR20; 46 percent of TREMFYA q4w patients and 48 percent of TREMFYA q8w patients achieved ACR50 (NRI).
• Among patients who had clinically relevant psoriasis at baseline, 84 percent of TREMFYA q4w patients, 77 percent of TREMFYA q8w patients and 84 percent of patients who crossed over from placebo to TREMFYA q4w achieved clear or almost clear skin with at least a 2 grade improvement from baseline as measured by the IGA score (observed data).⁶
• TREMFYA q4w and q8w demonstrated sustained improvements in inhibition of radiographic progression of joint structural damage through week 52 (observed data).⁷

The DISCOVER studies also showed improvements in multiple secondary endpoints at week 52 compared with week 24, including ACR70 response, resolution of soft tissue inflammation (enthesitis and dactylitis)^8,9, disease activity score (DAS-28) (C-Reactive Protein [CRP])¹⁰, (minimal disease activity [MDA])¹¹, (very low disease activity [VLDA])¹², improvement in physical function (Health Assessment Questionnaire Disability Index [HAQ-DI])¹³, general health outcomes (SF-36 Physical Component Summary [PCS] and Mental Component Summary [MCS]).^14,15,16 

In both studies, TREMFYA was well-tolerated through study completion, and observed adverse events (AEs) were generally consistent with previous studies of TREMFYA and current prescribing information.¹⁷ Serious AEs and serious infections occurred in 4 percent and 1 percent of TREMFYA-treated patients, respectively, in both DISCOVER-1 and DISCOVER-2. There were no reported deaths in TREMFYA-treated patients and no TREMFYA-treated patient had inflammatory bowel disease, opportunistic infections, active tuberculosis or anaphylactic or serum sickness-like reactions.^1,2

"Efficacy of TREMFYA in psoriatic arthritis was previously demonstrated to be superior to placebo at week 24. These new data show that efficacy is maintained to week 52 with safety data that are consistent with the well-established profile of TREMFYA in psoriasis," said Alyssa Johnsen, M.D., Ph.D., Vice President, Rheumatology Disease Area Leader, Janssen Research & Development, LLC. "We are excited to share the data on TREMFYA in psoriatic arthritis as we continue to advance our research in this disease and bring more treatment options to psoriatic arthritis patients in need."

In a separate study, data from DISCOVER-1 and DISCOVER-2 were analyzed as part of a network meta-analysis that compared the efficacy and safety of TREMFYA to other targeted biologic therapies for PsA. Twenty-six Phase 3 studies were included comparing the impact of 13 targeted therapies for PsA on ACR 20/50/70 response, Psoriasis Area Severity Index (PASI) 75/90/100 response, HAQ-DI score, resolution of enthesitis, resolution of dactylitis, AEs and serious AEs. The analysis is being shared as an abstract (Abstract AB0820) during the EULAR E-Congress.¹⁸

About DISCOVER-1 (NCT03162796)¹⁹
DISCOVER-1 is a randomized, double-blind, multicenter Phase 3 study evaluating the efficacy and safety of TREMFYA administered by subcutaneous (SC) injection in participants with active psoriatic arthritis including those previously treated with biologic anti-TNF alpha agent(s). DISCOVER-1 evaluated 381 participants and continued through approximately one year.⁴

The study consisted of a screening phase of up to six weeks, a blinded treatment phase of 52 weeks that includes a placebo-controlled period from week 0 to week 24 and an active treatment period from week 24 to week 52. It also includes a safety follow-up phase of eight weeks after week 52 (week 52 to 60; 12 weeks from the last administration of study agent [at week 48] through to the final visit in the safety follow-up phase). Efficacy, safety, pharmacokinetic, immunogenicity and biomarker evaluations were performed in the study on a defined schedule.

About DISCOVER-2 (NCT03158285)²⁰
DISCOVER-2 is a randomized, double-blind, multicenter Phase 3 study evaluating the efficacy and safety of TREMFYA administered by SC injection in subjects with active psoriatic arthritis. DISCOVER-2 is evaluating 739 participants and continuing through approximately two years.⁵

The study consists of a screening phase of up to six weeks, a blinded treatment phase (approximately 100 weeks) that includes a placebo-controlled period from week 0 to week 24 and an active treatment period from week 24 to week 100. It also includes a safety follow-up phase of 12 weeks after the last administration of study agent. Efficacy, health economics, safety, pharmacokinetics, immunogenicity, biomarker and pharmacogenomics evaluations are being performed in the study on a defined schedule.

About Psoriatic Arthritis
Psoriatic arthritis (PsA) is a chronic, immune-mediated inflammatory disease characterized by peripheral joint inflammation, enthesitis, dactylitis, axial disease and the skin lesions associated with psoriasis.²¹ Studies show that up to 30 percent of people with psoriasis also develop PsA.²² 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.^22,23 Though the exact cause of PsA is unknown, genes, the immune system and environmental factors are all believed to play a role in the onset of the disease.²³

About TREMFYA^® (guselkumab)¹⁷
Developed by Janssen, TREMFYA^® is the first approved human monoclonal antibody that selectively binds to the p19 subunit of IL-23 and inhibits its interaction with the IL-23 receptor. TREMFYA is approved in the U.S., Canada, the European Union, Japan and a number of other countries worldwide for the treatment of adult patients with moderate to severe plaque psoriasis who may benefit from taking injections or pills (systemic therapy) or phototherapy (treatment using ultraviolet [UV] light). It is approved as a prescription medicine in Japan and Brazil for the treatment of adult patients with active PsA. IL-23 is an important driver of the pathogenesis of inflammatory diseases such as psoriasis and PsA.²⁴

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^® may cause serious side effects, including infections. TREMFYA^® is a prescription medicine that 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:
• fever, sweats, or chills
• muscle aches
• weight loss
• cough
• warm, red, or painful skin or sores on your body different from your psoriasis
• diarrhea or stomach pain
• shortness of breath
• blood in your phlegm (mucus)
• 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^®?" 

Serious Allergic Reactions
Stop using TREMFYA^® and get emergency medical help right away if you have any of the following symptoms of a serious allergic reaction: feel faint, swelling of your face, eyelids, lips, mouth, tongue or throat, trouble breathing or throat tightness, chest tightness, or skin rash, hives.

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 and herpes simplex infections.

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. 

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 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 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 December 30, 2018, 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.

ⁱDr Christopher Ritchlin is a paid consultant for Janssen. He has not been compensated for any media work.

1. Ritchlin, C, et al. Guselkumab, an IL-23 Inhibitor That Specifically Binds to the IL23p19-Subunit, for   Active Psoriatic Arthritis: One Year Results of a Phase 3, Randomized, Double-blind, Placebo-controlled Study of Patients who Were Biologic-Naïve or TNFα Inhibitor-Experienced. SAT0397. Presented at the 2020 EULAR E-Congress June 3—6.
2. McInnes, I, et al. Efficacy and Safety of Guselkumab, a Monoclonal Antibody Specific to the p19-Subunit of Interleukin-23, Through Week 52 of a Phase 3, Randomized, Double-blind, Placebo-controlled Study Conducted in Biologic-naïve Patients with Active Psoriatic Arthritis. SAT0402. Presented at the 2020 EULAR E-Congress June 3—6.
3. Janssen.com. Janssen Submits Application to U.S. FDA Seeking First-in-Class Approval of TREMFYA^® (guselkumab) for Treatment of Active Psoriatic Arthritis. Available at: https://www.janssen.com/janssen-submits-application-us-fda-seeking-first-class-approval-tremfya-guselkumab-treatment-adults. Accessed May 2020.
4. 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, Randomized, Placebo-controlled Phase 3 Trial. The Lancet 2020 395:1115–1125.
5. Mease PJ, et al. Guselkumab in Biologic-naive Patients with Active Psoriatic Arthritis (DISCOVER-2): A Double-blind, Randomized, Placebo-controlled Phase 3 Trial. The Lancet 2020; 395:1126–1136.
6. Investigator Global Assessment score of 0 or 1, and a >2 grade reduction in body surface area affected.
7. The van der Heijde modified Sharpscore (modified for use in psoriatic arthritis) is a method used to assess and rate erosions and joint space narrowing in radiographs of hands and feet.
8. Pain where the bone, tendon and ligament meet.
9. Severe inflammation of the finger and toe joints.
10. Patients were considered to have achieved minimal disease activity if fulfilling at least five of the following seven criteria: tender joint count 1 or less, swollen joint count 1 or less, PASI score 1 or less, patient pain VAS score 15 or less, patient global disease activity VAS score 20 or less, HAQ-DI score 0.5 or less, and tender entheseal points 1 or less.
11. MDA is defined by low activity assessed by tender/swollen joint counts, tender entheseal points, Psoriasis Area and Severity Index or body surface area, patient pain and global activity visual analog scale, and functional evaluation by Health Assessment Questionnaire.
12. VLDA is defined as achieving all 7/7 MDA criteria.
13. HAQDI is a patient questionnaire that assesses physical function and disability across rheumatic diseases.
14. SF-36 is a patient-reported survey that measures functional health and wellbeing.
15. As part of SF-36, the PCS subscale is composed of four scales assessing physical function, role limitations caused by physical problems, bodily pain, and general health.
16. MCS is composed of four scales assessing vitality, emotional impact, social functioning, and mental health.
17. Food and Drug Administration. TREMFYA Prescribing Information. 2017. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761061s000lbl.pdf. Accessed May 2020.
18. McInnes, I, et al. Comparative Efficacy of Guselkumab in Patients with Psoriatic Arthritis: Results from Systemic Literature Review and Network Meta-Analysis. (AB0820). Presented at the 2020 EULAR E-Congress June 3—6.
19. Clinicaltrials.gov. A Study Evaluating the Efficacy and Safety of Guselkumab Administered Subcutaneously in Participants With Active Psoriatic Arthritis Including Those Previously Treated With Biologic Anti-Tumor Necrosis Factor (TNF) Alpha Agent(s) (DISCOVER-1). Identifier: NCT03162796. Available at: https://clinicaltrials.gov/ct2/show/NCT03162796. Accessed May 2020.
20. Clinicaltrials.gov. A Study Evaluating the Efficacy and Safety of Guselkumab Administered Subcutaneously in Participants With Active Psoriatic Arthritis (DISCOVER-2). Identifier: NCT03158285. Available at: https://clinicaltrials.gov/ct2/show/NCT03158285. Accessed May 2020.
21. Belasco J, Wei N. Psoriatic Arthritis: What is Happening at the Joint? Rheumatol Ther 2019 6:305-315.
22. National Psoriasis Foundation. Statistics. Available at: https://www.psoriasis.org/content/statistics Accessed May 2020.
23. National Psoriasis Foundation. About Psoriatic Arthritis. Available at: https://www.psoriasis.org/about-psoriatic-arthritis. Accessed May 2020.
24. Benson JM, et al. Discovery and Mechanism of Ustekinumab. MAbs 2011 3:535.

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