• Icotrokinra (JNJ-2113), a first-in-class investigational targeted oral peptide that selectively blocks the IL-23 receptor, met its co-primary endpoints in patients with moderate to severe plaque psoriasis
• 74% of patients achieved clear or almost clear skin (IGA 0/1) at week 24
• Comprehensive results are being prepared for presentation at upcoming medical congresses

SPRING HOUSE, Pa., Nov. 18, 2024 /PRNewswire/ -- Johnson & Johnson (NYSE: JNJ) today announced positive topline results from ICONIC-LEAD^a, a pivotal Phase 3 investigational study of icotrokinra (JNJ-2113), the first targeted oral peptide that selectively blocks the IL-23 receptor, in adults and adolescents 12 years of age and older with moderate to severe plaque psoriasis (PsO). The Phase 3 study met its co-primary endpoints of Psoriasis Area and Severity Index (PASI) 90^b and Investigator's Global Assessment (IGA) of 0/1^c response at week 16 and response rates continued to improve through week 24.¹

Once daily icotrokinra showed significant skin clearance versus placebo in adults and adolescents with moderate to severe plaque psoriasis. At week 16, nearly two-thirds (64.7%) of patients treated with icotrokinra achieved IGA scores of 0/1 (clear or almost clear skin), and 49.6% achieved PASI 90, compared to 8.3% and 4.4% on placebo, respectively.¹ Further increases in response rates continued to be observed at week 24, with 74.1% of patients treated with icotrokinra achieving IGA scores of 0/1, and 64.9% achieving PASI 90.¹ Safety data was found to be consistent with the Phase 2 FRONTIER 1 and 2 studies. A similar proportion of patients experienced adverse events (AEs) between icotrokinra and placebo, with 49.3% and 49.1% of participants experiencing a treatment emergent adverse event (TEAE) at week 16.^1,2,3

Furthermore, positive topline results from the Phase 3 ICONIC-TOTAL^d study showed once daily icotrokinra met the primary endpoint of IGA of 0/1 at week 16 compared to placebo.⁴ Comprehensive results from ICONIC-LEAD and ICONIC-TOTAL are being prepared for presentation at upcoming medical congresses and will be shared with health authorities in planned submissions.

"We are excited to see impressive Phase 3 results with once-daily icotrokinra treatment aligned with our Phase 2 study of this first-in-class targeted oral peptide that selectively blocks the IL-23 receptor," said Liza O'Dowd, Vice President, Immunodermatology Disease Area Lead, Johnson & Johnson Innovative Medicine. "The majority of people living with moderate to severe plaque psoriasis are eligible for, but are still not receiving, advanced therapies. Icotrokinra has the potential to offer once-daily oral therapy that could help address the needs and preferences of people living with plaque psoriasis."

Other studies in the Phase 3 ICONIC clinical development program are ongoing, including ICONIC-ADVANCE 1 and ICONIC-ADVANCE 2, which will evaluate the safety and efficacy of icotrokinra compared with both placebo and deucravacitinib in moderate to severe plaque PsO. The Phase 3 ICONIC-PsA program which will investigate icotrokinra in psoriatic arthritis will be initiated in the beginning of 2025.

Editor's notes

a. ICONIC-LEAD is a randomized controlled trial (RCT) to evaluate the safety and efficacy of icotrokinra compared with placebo in participants 12 years of age or older with moderate to severe plaque PsO, with the higher efficacy bar of PASI 90 and IGA score of 0/1 with at least a 2-grade improvement as co-primary endpoints. ICONIC-LEAD enrolled 66 adolescent patients.

b. The PASI score grades the amount of surface area on each body region that is covered by psoriasis plaques and the severity of plaques for their redness, thickness and scaliness.⁵ PASI 90 corresponds to an improvement of >=90% in PASI score from baseline.⁵

c. The IGA is a five-point scale with a severity ranging from 0 to 4, where 0 indicates clear, 1 is minimal, 2 is mild, 3 is moderate, and 4 indicates severe disease.⁶

d. ICONIC-TOTAL is a RCT to evaluate the efficacy and safety of icotrokinra compared with placebo for the treatment of PsO in participants with at least moderate severity affecting special areas (e.g., scalp, genital, and/or hands and feet) with overall IGA score of 0 or 1 with at least a 2-grade improvement as the primary endpoint.

About the ICONIC Clinical Development Program

The pivotal Phase 3 ICONIC clinical development program of icotrokinra (JNJ-2113) in adult and adolescent individuals with moderate to severe plaque PsO was initiated with two studies in Q4 2023 – ICONIC-LEAD and ICONIC-TOTAL – pursuant to the license and collaboration agreement between Protagonist Therapeutics, Inc. and Janssen Biotech, Inc.⁷

ICONIC-LEAD (NCT06095115) is a randomized controlled trial (RCT) to evaluate the safety and efficacy of icotrokinra compared with placebo in participants with moderate to severe plaque PsO, with PASI 90 and IGA score of 0 or 1 with at least a 2-grade improvement as co-primary endpoints.⁸

ICONIC-TOTAL (NCT06095102) is a RCT to evaluate the efficacy and safety of icotrokinra compared with placebo for the treatment of PsO in participants with at least moderate severity affecting special areas (e.g., scalp, genital, and/or hands and feet) with overall IGA score of 0 or 1 with at least a 2-grade improvement as the primary endpoint.⁹

Other Phase 3 studies in the development program include ICONIC-ADVANCE 1 (NCT06143878) and ICONIC-ADVANCE 2 (NCT06220604), which evaluate the safety and efficacy of icotrokinra compared with both placebo and deucravacitinib in adults with moderate to severe plaque PsO.¹⁰

About Plaque Psoriasis

Plaque psoriasis (PsO) is a chronic immune-mediated disease resulting in overproduction of skin cells, which causes inflamed, scaly plaques that may be itchy or painful.¹¹ It is estimated that eight million Americans and more than 125 million people worldwide live with the disease.¹² Nearly one-quarter of all people with plaque PsO have cases that are considered moderate to severe.¹² On Caucasian skin, plaques typically appear as raised, red patches covered with a silvery white buildup of dead skin cells or scale.¹³ On skin of color, the plaques may appear darker and thicker and more of a purple, gray or dark brown color.¹³ Plaques can appear anywhere on the body, although they most often appear on the scalp, knees, elbows, and torso.¹³ 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.¹⁴ Psoriasis on highly visible areas of the body or sensitive skin, such as the scalp, hands, feet, and genitals, can have an increased negative impact on quality of life.^13,15

About Icotrokinra (JNJ-77242113, JNJ-2113)

Investigational icotrokinra is the first targeted oral peptide designed to selectively block the IL-23 receptor,³ which underpins the inflammatory response in moderate to severe plaque PsO and other IL-23-mediated diseases.^16,17 Icotrokinra binds to the IL-23 receptor with single-digit picomolar affinity and demonstrated potent, selective inhibition of IL-23 signaling in human T cells.¹⁸ The license and collaboration agreement established between Protagonist Therapeutics, Inc. and Janssen Biotech, Inc., in 2017 enabled the companies to work together to discover and develop next-generation compounds that ultimately led to icotrokinra.¹⁹ Icotrokinra was jointly discovered and is being developed pursuant to the license and collaboration agreement between Protagonist and Johnson & Johnson. Johnson & Johnson retains exclusive worldwide rights to develop icotrokinra in Phase 2 clinical trials and beyond, and to commercialize compounds derived from the research conducted pursuant to the agreement against a broad range of indications.^20,21,22

About Johnson & Johnson

At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity.

Learn more at https://www.jnj.com/ or at www.innovativemedicine.jnj.com. Follow us at @JNJInnovMed.

Janssen Research & Development, LLC and Janssen Biotech, Inc. are Johnson & Johnson companies.

Cautions Concerning Forward-Looking Statements

This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding icotrokinra (JNJ-2113). 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, Janssen Biotech, Inc. 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 31, 2023, including in the sections captioned "Cautionary Note Regarding Forward-Looking Statements" and "Item 1A. Risk Factors," and in Johnson & Johnson's subsequent Quarterly Reports on Form 10-Q and other 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 Janssen Research & Development, LLC, Janssen Biotech, Inc. nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.

¹ Data on file.
² Ferris, L et al. A Phase 2b, Long-term Extension, Dose-ranging Study of Oral JNJ-77242113 for the Treatment of Moderate to Severe Plaque Psoriasis: FRONTIER 2. Oral presentation (Abstract #S026) at the American Academy of Dermatology (AAD) 2024 Annual Meeting. March 2024.
³ Bissonnette R, et al. Data presentation. A phase 2, randomized, placebo-controlled, dose-ranging study of oral JNJ-77242113 for the treatment of moderate to severe plaque psoriasis: FRONTIER 1. Presented at WCD 2023, July 3-8.
⁴ Data on file.
⁵ Thompson Jr, D. How the Psoriasis Area and Severity Index works. Everyday Health. Available at: https://www.everydayhealth.com/psoriasis/living-with/how-the-pasi-index-works. Accessed November 2024.
⁶ Simpson E, Bissonnette R, Eichenfield LF, et al. The validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD™): The development and reliability testing of a novel clinical outcome measurement instrument for the severity of atopic dermatitis [published online April 25, 2020]. J Am Acad Dermatol. doi: 10.1016/j.jaad.2020.04.104. Accessed November 2024.
⁷ Protagonist Therapeutics. Press release. Protagonist announces advancement of JNJ-2113 across multiple indications. Available at: https://www.accesswire.com/791174/protagonist-announces-advancement-of-jnj-2113-across-multiple-indications. Accessed November 2024.
⁸ Clinicaltrials.gov. A study of JNJ-2113 in adolescent and adult participants with moderate to severe plaque psoriasis (ICONIC-LEAD). Identifier NCT06095115. https://classic.clinicaltrials.gov/ct2/show/NCT06095115. Accessed November 2024.
⁹ Clinicaltrials.gov. A study of JNJ-2113 for the treatment of participants with plaque psoriasis involving special areas (scalp, genital, and/or palms of the hands and the soles of the feet) (ICONIC-TOTAL). Identifier NCT06095102. https://classic.clinicaltrials.gov/ct2/show/NCT06095102. Accessed November 2024.
¹⁰ Protagonist Therapeutics. Press release. Protagonist announces two new phase 3 ICONIC studies in psoriasis evaluating JNJ-2113 in head-to-head comparisons with deucravacitinib. Available at: https://www.accesswire.com/810075/protagonist-announces-two-new-phase-3-iconic-studies-in-psoriasis-evaluating-jnj-2113-in-head-to-head-comparisons-with-deucravacitinib. Accessed November 2024.
¹¹ National Psoriasis Foundation. About Psoriasis. Available at: https://www.psoriasis.org/about-psoriasis. Accessed November 2024.
¹² National Psoriasis Foundation. Psoriasis Statistics. Available at: https://www.psoriasis.org/content/statistics. Accessed November 2024.
¹³ National Psoriasis Foundation. Plaque Psoriasis. Available at: https://www.psoriasis.org/plaque/.Accessed November 2024.
¹⁴ National Psoriasis Foundation. Life with Psoriasis. Available at: https://www.psoriasis.org/life-with-psoriasis/. Accessed November 2024.
¹⁵ National Psoriasis Foundation. High Impact Sites. Available at: https://www.psoriasis.org/high-impact-sites/. Accessed Sep November 2024.
¹⁶ Razawy W, et al. The role of IL–23 receptor signaling in inflammation–mediated erosive autoimmune arthritis and bone remodeling. Eur J Immunol. 2018 Feb; 48(2): 220–229.
¹⁷ Tang C, et al. Interleukin-23: as a drug target for autoimmune inflammatory diseases. Immunology. 2012 Feb; 135(2): 112–124.
¹⁸ Pinter A, et al. Data Presentation. JNJ-77242113 Treatment Induces a Strong Systemic Pharmacodynamic Response Versus Placebo in Serum Samples of Patients with Plaque Psoriasis: Results from the Phase 2, FRONTIER 1 Study. Presented at EADV 2023, October 11-14.
¹⁹ Johnson & Johnson. Press release. Janssen enters into worldwide exclusive license and collaboration agreement with Protagonist Therapeutics, Inc. for the oral Interlukin-23 receptor antagonist drug candidate for the treatment of Inflammatory Bowel Disease. Available at: https://www.jnj.com/media-center/press-releases/janssen-enters-into-worldwide-exclusive-license-and-collaboration-agreement-with-protagonist-therapeutics-inc-for-the-oral-interlukin-23-receptor-antagonist-drug-candidate-for-the-treatment-of-inflammatory-bowel-disease. Accessed November 2024.
²⁰ Protagonist Therapeutics. Press release. Protagonist Therapeutics announces amendment of agreement with Janssen Biotech for the continued development and commercialization of IL-23 antagonists. Available at: https://www.prnewswire.com/news-releases/protagonist-therapeutics-announces-amendment-of-agreement-with-janssen-biotech-for-the-continued-development-and-commercialization-of-il-23-antagonists-301343621.html. Accessed November 2024.
²¹ Protagonist Therapeutics. Press release. Protagonist Reports positive results from Phase 1 and pre-clinical studies of oral Interleukin-23 receptor antagonist JNJ-2113. Available at: https://www.prnewswire.com/news-releases/protagonist-reports-positive-results-from-phase-1-and-pre-clinical-studies-of-oral-interleukin-23-receptor-antagonist-jnj-2113-301823039.html. Accessed November 2024.
²² Protagonist Therapeutics. Press release. Protagonist Therapeutics announces positive topline results for Phase 2b FRONTIER 1 clinical trial of oral IL-23 receptor antagonist JNJ-2113 (PN-235) in psoriasis. Available at: https://www.prnewswire.com/news-releases/protagonist-therapeutics-announces-positive-topline-results-for-phase-2b-frontier-1-clinical-trial-of-oral-il-23-receptor-antagonist-jnj-2113-pn-235-in-psoriasis-301764181.html. Accessed November 2024.