New Comprehensive Phase 3 Data Show First-in-Class TREMFYA® (guselkumab) Provided Durable Improvements in Measures of Psoriatic Arthritis (PsA) Disease Activity Through Two Years

SPRING HOUSE, Pa., Nov. 1, 2021 /PRNewswire/ -- The Janssen Pharmaceutical Companies of Johnson & Johnson today announced comprehensive efficacy and safety data from the DISCOVER–2 trial of TREMFYA^® (guselkumab) were published in Arthritis & Rheumatology, representing the final results of the first two-year clinical trial investigating a selective interleukin (IL)-23 inhibitor therapy in active psoriatic arthritis (PsA).¹ Results show a majority of TREMFYA-treated biologic-naïve adult patients with active PsA achieved improvements in joint signs and symptoms (American College of Rheumatology [ACR] 20/50/70)^a and complete skin clearance (Investigator's Global Assessment [IGA] 0)^b that were maintained or increased over time, suggesting continued TREMFYA treatment may lead to higher levels of symptom improvement. TREMFYA demonstrated low rates of radiographic progression,^c a key indicator of structural damage, which includes erosion and joint space narrowing, and provided substantial and durable improvements across multiple additional disease domains, including achievement of minimal disease activity (MDA)^d and normalized physical function (Health Assessment Questionnaire Disability Index [HAQ-DI] ≤0.5).^1,2,e

"These comprehensive, two-year data yield important insights into how patients with psoriatic arthritis can achieve and sustain improvements across symptoms with the ultimate goal being full remission," said study investigator Philip Mease,^f M.D., Director of Rheumatology Research at the Swedish Medical Center/Providence St. Joseph Health and Clinical Professor at the University of Washington School of Medicine. "It's helpful for both healthcare providers and patients to understand the long-term profile of therapies like TREMFYA in order to make informed decisions about treatment for a life-long disease like psoriatic arthritis."

The data from the study show durable improvement in joint manifestations and skin clearance:¹  

• Among TREMFYA patients who achieved an ACR20, ACR50, or ACR70 response at week 52, 91 percent of patients receiving treatment every four weeks (q4w)^g and 87 percent of patients receiving treatment every eight weeks (q8w) maintained an ACR20 response at week 100. Eighty-three percent of q4w and 79 percent of q8w patients maintained an ACR50 response, and 72 percent and 80 percent maintained an ACR70 response.
• In both TREMFYA groups, ACR response rates were maintained or continued to improve through week 100. Response rates for ACR50 and ACR70 increased through the second year of treatment, suggesting that individual patients may be improving over time and achieving higher levels of improvement with continued TREMFYA treatment.
• Low rates of radiographic progression, a key indicator of structural damage, were seen from week 0–100 across both TREMFYA dosing regimens.^h Mean changes in total van der Heijde Modified Sharp (vdH-S)ⁱ scores indicated less radiographic progression from week 52–100 than from week 0–52 in all three treatment groups (q4w, q8w, and patients who crossed over from placebo to TREMFYA at week 24).
• Enthesitis and dactylitis resolution rates at week 100 showed amelioration of these signs and symptoms of arthritis was durable through two years. Among patients affected at baseline, 62 percent in the q4w group and 70 percent in the q8w group achieved complete resolution of enthesitis and 72 percent and 83 percent, respectively, achieved complete resolution of dactylitis at week 100.
• Among patients receiving TREMFYA from week 0, 62 percent and 55 percent of patients in the q4w and q8w groups, respectively, achieved complete skin clearance (IGA score of 0) at week 100, and 76 percent and 72 percent had an IGA score of 0/1 (clear/almost clear).^j

TREMFYA also demonstrated durable improvements in physical function and maintenance of low disease activity:¹

• At week 100, 38 percent and 40 percent of patients receiving TREMFYA q4w and q8w, respectively, achieved the more stringent criteria of minimal disease activity (MDA).^d Among patients achieving MDA at week 52, 81 percent and 83 percent in the q4w and q8w groups, respectively, maintained MDA at week 100. In addition, 14 percent of patients in the q4w group and 17 percent in the q8w group achieved very low disease activity (VLDA).^k
• At week 100, least squares mean changes from baseline in the HAQ-DI^e in the q4w (–0.55) and q8w (-0.53) groups were consistent with those at week 52, and 63 to 64 percent of patients receiving either dosing regimen reported a clinically meaningful improvement in HAQ-DI scores (≥0.35). Additionally, 35 to 40 percent of patients in the TREMFYA groups reported normalized physical function (HAQ-DI ≤0.5) at week 100.

DISCOVER-2 data, which represent the most comprehensive results for a selective IL-23 inhibitor in PsA patients, also showed consistency in the established safety profile of TREMFYA:¹

• Adverse events (AEs) through two years of DISCOVER-2 were consistent with those reported through one year of DISCOVER-2 and those seen in the one-year DISCOVER-1 study and in the five-year VOYAGE 1 and 2 studies in plaque PsO.^3-6 TREMFYA-treated patients exhibited low rates of infections (37.3 events/100 patient-years of follow-up), serious infections (1.9 events/100 patient-years of follow-up), and opportunistic infections (in three patients with predisposing factors during the second year of treatment). Among all patients, there were no cases of active tuberculosis, and in TREMFYA-treated patients there were no cases of inflammatory bowel disease.
• TREMFYA-treated patients also receiving methotrexate (MTX) had numerically higher rates of elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, which can indicate abnormal liver function, than patients not receiving MTX. PsA patients often receive concomitant therapy with MTX and oral corticosteroids, in contrast with PsO patients.⁷

"The response rates in the DISCOVER-2 trial demonstrate the ability of TREMFYA to improve the signs and symptoms of psoriatic arthritis for people who live with the challenges of this disease," said Alyssa Johnsen, M.D., Ph.D., Vice President and Rheumatology Disease Area Leader, Janssen Research & Development, LLC. "Psoriatic arthritis is a chronic disease, so patients need treatment options with durable efficacy and an established safety profile. We are proud to deliver the first two-year results for a selective IL-23 inhibitor therapy in PsA."

Janssen's continued commitment to advancing TREMFYA for the treatment of active PsA is demonstrated by the TREMFYA PsA clinical development program, which currently includes two studies in Phase 3b, NCT04882098 and NCT04936308, and one in Phase 4 testing, NCT04929210.^8,9,10

Editor's Note:
a. 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, patient-reported functional ability (HAQ-DI), patient-reported pain using a visual analogue, and a laboratory marker of systemic inflammation (erythrocyte sedimentation rate or C-reactive protein level).¹¹
b. IGA is a five-point scoring system used to characterize PsO severity. Scores range from 0 to 5 and represent cleared (0), almost clear (1), mild (2), moderate (3), severe (4), and very severe (5) skin PsO.¹²
c. Radiographic progression is not in the U.S. Food and Drug Administration (FDA) label for TREMFYA.¹³
d. MDA is defined as low disease activity across five of the following seven domains of PsA: tender joint count, swollen joint count, tender entheses, Psoriasis Area and Severity Index (PASI) or body surface area affected with PsO, patient pain assessment and global disease activity assessments, and patient-reported physical function.¹⁴
e. HAQ-DI is a patient questionnaire that assesses physical function and disability across rheumatic diseases.¹⁵ Normalized physical function is defined as a HAQ-DI score ≤0.5. These results were seen among patients with HAQ-DI ≥0.35 and ≥0.5 at baseline.
f. Dr. Mease is a paid consultant for Janssen. He was not compensated for any media work.
g. TREMFYA is approved for administration as a 100-mg subcutaneous (SC) injection given every eight weeks, following initial doses at weeks 0 and 4.¹³
h. TREMFYA is not FDA-approved for inhibition of structural damage.
i. The total PsA-modified vdH-S score is a composite score of structural damage that ranges from 0-528 and measures the number and size of joint erosions and the degree of joint space narrowing in the hands and feet.² The vdH-S score is not in the U.S. FDA label for TREMFYA.
j. These results were seen among patients with PsO body surface area ≥3 percent and IGA ≥2 at baseline.¹
k. VLDA (considered "remission") represents low disease activity across all seven of the MDA components noted above.¹⁶

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.^17-19 In addition, in patients with PsA, comorbidities, such as obesity, cardiovascular diseases, anxiety and depression are often present.²⁰ Studies show up to 30 percent of people with plaque PsO also develop PsA.²¹ 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.²¹ 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.²² 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.²³

About Psoriasis (PsO)
Plaque PsO is an immune-mediated disease resulting in an overproduction of skin cells, which causes raised, red, scaly plaques that may be itchy or painful.²⁴ It is estimated that more than 125 million people worldwide live with the disease.²⁴ Nearly one-quarter of all people with plaque PsO have cases that are considered moderate to severe.²⁵ Living with plaque PsO can be a challenge and impact life beyond a person's physical health, including emotional health, relationships, and handling the stressors of life.²⁶

About DISCOVER-2 (NCT03158285)²⁷
DISCOVER-2 is a randomized, double-blind, multicenter Phase 3 study evaluating the efficacy and safety of TREMFYA administered by subcutaneous (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 was previously presented at scientific congresses. 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 Survey Physical Component Summary and Mental Component Score). 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 TREMFYA^® (guselkumab)¹³
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.²⁸ 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:
  • fainting, dizziness, feeling lightheaded (low blood pressure)
  • swelling of your face, eyelids, lips, mouth, tongue or throat
  • trouble breathing or throat tightness
  • chest tightness
  • skin rash, hives
  • 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:

•  
  • 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^®?"

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.

References

1. McInnes I, et al. Long-term Efficacy and Safety of Guselkumab, a Monoclonal Antibody Specific to the p19 Subunit of Interleukin-23, Through 2 Years: Results from a Phase 3, Randomized, Double-blind, Placebo-controlled Study Conducted in Biologic-naïve Patients with Active Psoriatic Arthritis. Arthritis & Rheumatology.
2. van der Heijde D, et al. Assessing structural damage progression in psoriatic arthritis and its role as an outcome in research. Arthritis Res Ther. 2020;22(1):18.
3. McInnes I, et al. Efficacy and Safety of Guselkumab, an Interleukin–23p19–Specific Monoclonal Antibody, Through One Year in Biologic–Naive Patients With Psoriatic Arthritis. Arthritis & Rheumatology. 73.4 (2021): 604-616.
4. Rahman P, et al. Pooled Safety Results Through One Year of Two Phase-3 Trials of Guselkumab in Patients with Psoriatic Arthritis. The Journal of Rheumatology. 2021.
5. Blauvelt A, et al. 28095 Long-term safety of guselkumab: Results from the VOYAGE 1 and VOYAGE 2 trials with up to 5 years of treatment. Journal of the American Academy of Dermatology. 85.3 (2021): AB174.
6. Rahman P, et al. FRI0359 Integrated Safety Results Of Two Phase-3 Trials Of Guselkumab In Patients With Psoriatic Arthritis Through The Placebo-Controlled Periods. 2020;776-777.
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8. ClinicalTrials.gov. A Study of Guselkumab in Participants With Active Psoriatic Arthritis (APEX). Available at: https://clinicaltrials.gov/ct2/show/NCT04882098. Accessed October 2021.
9. ClinicalTrials.gov. Guselkumab in Active Psoriatic Arthritis Participants With Inadequate Response/Intolerance to One Prior Anti-TNF Alpha Agent (SOLSTICE). Available at: https://clinicaltrials.gov/ct2/show/NCT04936308. Accessed October 2021.
10. ClinicalTrials.gov. A Study of Guselkumab Administered Subcutaneously in Bio-naive Participants With Active Psoriatic Arthritis Axial Disease (STAR). Available at: https://clinicaltrials.gov/ct2/show/NCT04929210. Accessed October 2021.
11. Felson DT and LaValley MP. The ACR20 and defining a threshold for response in rheumatic diseases: too much of a good thing. Arthritis Research & Therapy. 2014;16(1):101.
12. Langley R, et al. The 5-point Investigator's Global Assessment (IGA) Scale: a modified tool for evaluating plaque psoriasis severity in clinical trials. Journal of Dermatological Treatment 26.1 (2015): 23-31.
13. 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 Oct 11, 2021.
14. Coates LC, et al. Defining minimal disease activity in psoriatic arthritis: a proposed objective target for treatment. Ann Rheum Dis 2010;69:48-53.
15. Bruce B and Fries, JF. The Stanford Health Assessment Questionnaire: Dimensions and Practical Applications. Health and Quality of Life Outcomes. 2003;1(1) 20.
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17. Belasco J and Wei N. Psoriatic Arthritis: What is Happening at the Joint? Rheumatology and Therapy, 2019;6(3), 305–315.
18. Donvito T. CreakyJoints: What Is Enthesitis? The Painful Arthritis Symptom You Should Know About. Available at: https://creakyjoints.org/symptoms/what-is-enthesitis/. Accessed October 2021.   
19. 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.     
20. Haddad A and Zisman D. Comorbidities in Patients with Psoriatic Arthritis. Rambam Maimonides Med J. 2017;8(1):e0004.
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28. Benson JM, et al. Discovery and Mechanism of Ustekinumab. MAbs 2011;3:535.

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SOURCE Janssen Pharmaceutical Companies of Johnson & Johnson

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