Adults with moderately-to-severely active Sjögren's disease who received investigational FcRn blocker, nipocalimab, had improvements in disease activity scores at 24 weeks with accompanying significant reductions in IgG and autoantibody levels

Nipocalimab was granted U.S. FDA Breakthrough Therapy Designation for the treatment of adults living with moderate-to-severe Sjögren's disease based on results from the Phase 2 DAHLIAS study

BEERSE, BELGIUM, Nov. 14, 2024 (GLOBE NEWSWIRE) --  - Janssen-Cilag International NV, a Johnson & Johnson company, today announced results from additional analyses of the Phase 2 DAHLIAS study highlighting improvement in key measures of disease activity and associated IgG reductions by over 77% following treatment with investigational nipocalimab in adult patients with moderate-to-severe Sjögren's disease (SjD). These data were included in a plenary session presentation (Abstract #2527) and two posters (Abstract #s 1427 and 2294) and are among the Company's 43 oral and poster presentations at the American College of Rheumatology (ACR) Convergence 2024 taking place from November 14 to November 19 in Washington, D.C.^1,2

Patients receiving nipocalimab (n=54), an investigational FcRn blocker, showed a significant improvement in the ClinESSDAI^a score at 24 weeks, compared to placebo, achieving the primary endpoint of the study.^1,b Additionally, key secondary endpoints were met, indicating reduced disease activity both systemically and across multiple organ systems, as well as positive physician assessments and composite SjD assessment tools.¹

"These data highlight the relevance of autoantibodies in SjD pathogenesis. The observed reduction in IgG and pivotal autoantibodies, particularly anti-Ro antibodies, in association with improvement in systemic disease activity and saliva production, represent an exciting advance in our understanding of the disease and how it may be treated effectively. I am also encouraged by the observed trend in many patient-reported results shared at ACR, including positive trends in disease measures that are most important to patients, I look forward to future research to confirm these observations.” said Ghaith Noaiseh M.D., Associate Professor, Allergy, Clinical Immunology, and Rheumatology, The University of Kansas Medical Center.^e "People living with SjD need targeted treatment options that can help address the underlying causes and alleviate the potentially serious health consequences of the disease.” 

Results also showed a significant reduction in IgG including autoantibody levels among patients receiving 15 mg/kg (n=54) every two weeks, compared to placebo, providing further evidence of nipocalimab's mechanism of action.^1,c Moreover, improvements in ClinESSDAI were generally greatest in the participants with the highest baseline levels of anti-Ro and anti-La autoantibodies, associated with substantial nipocalimab-induced reductions in IgG and total IgG autoantibodies.^1,d

Nipocalimab was well-tolerated over the six-month study period, with no major safety signals observed. The most common adverse events (AEs) were infections and infestations: 60.4% (n=32) in the nipocalimab 5mg/kg group, 51.9% (n=28) in the nipocalimab 15mg/kg group, and 42.9% (n=24) in the placebo group.¹

Many people living with SjD experience symptoms that interfere with daily activities and quality of life, including chronic and severe mucosal dryness.^3,4 Extraglandular manifestations - more systemic symptoms of SjD - are also common and may impact multiple organ systems, including joints, lungs, kidneys, and nervous system.⁵ These patients with high activity in more than one organ or disease area have an increased mortality risk of up to five-fold.⁶

"For the estimated 175,000 people in Europe impacted by Sjögren's disease, symptoms such as mucosal dryness, skin rashes, joint pain and fatigue place a significant burden on their day-to-day lives,” said Ludovic de Beaucoudrey, Ph.D., Senior Director, Therapeutic Area Lead, Immunology, Janssen-Cilag Limited, a company of Johnson & Johnson. "We are excited by the potential clinical benefit of nipocalimab in SjD, and with these promising results, we are moving closer to providing adults living with SjD a new, targeted treatment option.”

In the Phase 2 study, patients reported a decrease in symptoms, with numerical improvements^f compared with placebo in the symptom categories most important to them, including mouth dryness, eye dryness, vaginal dryness, fatigue, and joint pain.^1,7 Additionally, an improvement in objective salivary flow (i.e., at least 50% increase from baseline) was observed in more than twice as many patients in the high dose nipocalimab group (15 mg/kg) compared to placebo (32% vs. 16%) at Week 24.¹

"No advanced therapies have been approved for Sjögren's disease to date. A clear unmet need exists for new immunoselective treatments with demonstrated safety profiles that can provide sustained relief from the heavy burden of the overall disease for patients living with SjD,” said Federico Zazzetti, Director, Rheumatology, Global Medical Affairs Lead, Johnson & Johnson Innovative Medicine. "Johnson & Johnson is committed to continued research to help address this unmet need, and the data presented at ACR demonstrate the potential of nipocalimab in a disease where patients have very few options.” 

Editor's Notes:

1. ClinESSDAI is an endpoint specific to SjD and is a composite scale that assesses organ disease activity across 11 organ system domains [cutaneous, pulmonary, renal, articular, muscular, peripheral nervous system (PNS), central nervous system (CNS), haematological, glandular, constitutional, lymphadenopathy and lymphoma]; a higher score indicates greater symptom severity.¹
2. Patients treated with nipocalimab (n=54) 15mg/kg achieved significantly greater reduction in ClinESSDAI score from baseline at week 24 versus placebo (Least square (LS) mean [90% confidence interval (CI)], -6.40 vs -3.74; P=0.002).¹
3. Patients treated with nipocalimab (n=30) 15mg/kg achieved a median (interquartile range [IQR]) reduction of 77% and observed predose (minimum) medium reduction of 61% in total IgG at Week 24, compared to placebo.¹
4. Improvements in the ClinESSDAI were greater in participants with high levels of autoantibodies. At Week 24, there was a LS mean (90% CI) treatment difference of -3.47 (-5.84 to -1.11) in the group with high autoantibody levels compared with -2.11 (-4.84 to 0.63) in the group with low autoantibody levels with nipocalimab 15mg/kg.¹
5. Ghaith Noaiseh, M.D. Ph.D., is a paid consultant for Johnson & Johnson. He has not been compensated for any media work.
6. Patients treated with nipocalimab (n=54) 15mg/kg achieved numerically greater reductions from baseline in ESSPRI score from Week 12 through Week 24 [LS Mean difference of -0.41; 90% CI; P=0.268] versus placebo.¹

Sjögren's disease (SjD) is one of the most prevalent autoantibody-driven diseases for which no therapies are currently approved that treat the underlying and systemic nature of the disease.⁸ It is a chronic autoimmune disease that is estimated to impact approximately four million people worldwide (175,000 people in Europe) and is nine times more common in women than men.^9,10,11 SjD is characterised by autoantibody production, chronic inflammation, and lymphocytic infiltration of exocrine glands.⁸ Most patients are affected by mucosal dryness (eyes, mouth, vagina), joint pain and fatigue.¹² More than 50% of SjD patients have a moderate to severe form of the condition, and disease burden can be as high as that of rheumatoid arthritis or systemic lupus erythematosus and is often associated with impaired quality of life and functional capacity, and increased mortality risk.^5,9,13

ABOUT DAHLIAS

DAHLIAS (NCT04969812) is a Phase 2 multicentre, randomised, placebo-controlled double-blind study to evaluate the effects of nipocalimab in participants with primary SjD.¹⁴ DAHLIAS is a Phase 2 dose-ranging study of adults with moderately-to-severely active primary SjD who were seropositive for anti-Ro60 and/or anti-Ro52 IgG antibodies.¹ 163 adults aged 18-75 were randomised 1:1:1 to receive intravenous nipocalimab at 5 or 15 mg/kg or placebo every two weeks through Week 22 and received protocol-permitted background standard of care. Safety assessments were conducted through Week 30.¹ The primary endpoint was change in baseline in the clinESSDAI Score at Week 24. Select secondary endpoints included:¹

• Multiple organ system assessments:
  • European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI) is a systemic diseases activity index designed to measure disease activity in patients with primary SjD. It is based on 12 domains including: constitutional, lymphadenopathy, glandular, articular, cutaneous, respiratory, renal, muscular, peripheral nervous system, central nervous system, biological, and haematological.¹
  • Disease Activity Level (DAL) response is a reduction from baseline in disease activity level by at least one level in at least one clinESSDAI domain (e.g., articular, haematological, cutaneous, constitutional).
• Physician assessment:
  • The Physician Global Assessment of Disease Severity (PhGA) is recorded by the investigator, independent of study participants' assessment, on a scale with responses ranging from 0 ("No SjD activity") to 100 ("Extremely active SjD").¹⁵ 
• Composite tools for clinical trial endpoints:
  • Sjögren's Tool for Assessing Response (STAR) is a composite responder index that includes all main SjD features, including systemic disease activity, patient-reported symptoms, tear gland item, salivary gland item and serology, in a single tool.¹⁶
  • Composite of Relevant Endpoints for Sjogren's Syndrome (CRESS), a composite endpoint tool consisting of five complementary items: systemic disease activity, patient-reported symptoms, tear gland item, salivary gland item and serology, for use in trials of primary SjD.¹⁷
• Patient reported outcomes:
  • European League Against Rheumatism Sjögren's Syndrome Patient-Reported Index (ESSPRI) is a patient-reported assessment of the severity of dryness, fatigue, and pain associated with primary SjD, in which patients report their symptom severity over the last two weeks on a numeric rating scale (NRS), ranging from 0 "No symptoms (dryness, fatigue or pain)” to 10 "maximal imaginable (dryness, fatigue, pain)”.^1,7
  • Sjögren's Symptoms tool is a patient-reported assessment of the worst severity of their ocular, oral, and vaginal dryness and joint pain over the past 7 days on a 0 to 10 NRS, from 0 "No [specific symptom]” to 10, "Severe [specific symptom]”.^1,18

Nipocalimab is an investigational monoclonal antibody, designed to bind with high affinity to block FcRn and reduce levels of circulating immunoglobulin G (IgG) antibodies potentially without impact on other immune functions.¹⁹ This includes autoantibodies and alloantibodies that underlie multiple conditions across three key segments in the autoantibody space including Rare Autoantibody diseases, Maternal Foetal diseases mediated by maternal alloantibodies and Prevalent Rheumatology. ^{20,21,22,23,24,25,26,27,28} Blockade of IgG binding to FcRn in the placenta is also believed to limit transplacental transfer of maternal alloantibodies to the foetus. ²⁹

The European Medicines Agency (EMA) and U.S. Food and Drug Administration (FDA) have granted several key designations to nipocalimab including:   

• EU EMA Orphan medicinal product designation for HDFN in October 2019 
• U.S. FDA Fast Track designation in haemolytic disease of the foetus and newborn (HDFN) and warm autoimmune haemolytic anaemia (wAIHA) in July 2019, gMG in December 2021 and foetal neonatal alloimmune thrombocytopenia (FNAIT) in March 2024
• U.S. FDA Orphan drug status for wAIHA in December 2019, HDFN in June 2020, gMG in February 2021, chronic inflammatory demyelinating polyneuropathy (CIDP) in October 2021 and FNAIT in December 2023
• U.S. FDA Breakthrough Therapy designation for HDFN in February 2024 by the FDA and for SjD in November 2024

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 www.innovativemedicine.jnj.com/emea/.

Follow us at www.linkedin.com/jnj-innovative-medicine-emea.

Janssen-Cilag International NV and Janssen-Cilag Limited are both 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 product development and the potential benefits and treatment impact of nipocalimab. 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., Janssen-Cilag International NV, Janssen-Cilag Limited, LLC 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 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., Janssen-Cilag International NV, Janssen-Cilag Limited, LLC 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:

² Johnson & Johnson. Johnson & Johnson advances leadership in rheumatic disease innovation with 43 abstracts at ACR 2024. Available at: https://www.jnj.com/media-center/press-releases/johnson-johnson-advances-leadership-in-rheumatic-disease-innovation-with-43-abstracts-at-acr-2024. Last accessed: November 2024

³ Sjogren's Disease Foundation. Understanding Sjogren's - Treatment. Available at: https://sjogrens.org/understanding-sjogrens/symptoms. Last accessed: November 2024.

⁴ McCoy SS, Woodham M, Bunya VY, Saldanha IJ, Akpek EK, Makara MA, Baer AN. A comprehensive overview of living with Sjögren's: results of a National Sjögren's Foundation survey. Clin Rheumatol. 2022 Jul;41(7):2071-2078. doi: 10.1007/s10067-022-06119-w. Epub 2022 Mar 8. PMID: 35257256; PMCID: PMC9610846

⁵ Carsons SE, Patel BC. Sjogren Syndrome. [Updated 2023 Jul 31]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK431049/

⁶ Brito-Zeron, P., et al. Mortality risk factors in primary Sjogren syndrome: a real-world, retrospective, cohort study. eClinicalMedicine. July, 4, 2023. DOI: https://doi.org/10.1016/j.eclinm.2023.102062

⁷ Seror R, et al. EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI): development of a consensus patient index for primary Sjogren's syndrome. Ann Rheum Dis. 2011 Jun;70(6):968-72. doi: 10.1136/ard.2010.143743. 

⁸ Huang H, Xie W, Geng Y, Fan Y, Zhang Z. Mortality in patients with primary Sjögren's syndrome: a systematic review and meta-analysis. Rheumatology (Oxford). 2021 Sep 1;60(9):4029-4038. doi: 10.1093/rheumatology/keab364. PMID: 33878179.

⁹ Nat Rev Rheumatol 20, 158-169 (2024). https://doi.org/10.1038/s41584-023-01057-6 

¹⁰ Seror R, et al. Estimated prevalence, incidence and healthcare costs of Sjögren's syndrome in France: a national claims-based study. RMD Open. 2024 Feb 2;10(1):e003591. doi: 10.1136/rmdopen-2023-003591.

¹¹ Eurostat. EU population increases again in 2024. Available at: https://ec.europa.eu/eurostat/web/products-eurostat-news/w/ddn-20240711-1. Last accessed: November 2024.

¹² Mayo Clinic. Sjogren's syndrome. Available at: https://www.mayoclinic.org/diseases-conditions/sjogrens-syndrome/symptoms-causes/syc-20353216. Last accessed: November 2024.

¹³ Hackett KL, et al. Arthritis Care Res (Hoboken). 2012;64(11):1760-1764.

¹⁴ ClinicalTrials.gov Identifier: NCT04968912. Available at: https://clinicaltrials.gov/study/NCT04968912. Last accessed: November 2024.

¹⁵ Assess Child. Physician Global Assessment (PGA). Available at: https://assesschild.com/physician-global-assessment. Last accessed: November 2024.

¹⁶ EMA. Letter of support for Sjogren's Tool for Assessing Response (STAR). Available at: https://www.ema.europa.eu/en/documents/other/letter-support-sjogrens-tool-assessing-response-star_en.pdf. Last accessed: November 2024.

¹⁷ Arends S, de Wolff L, Van Nimwegen JF, et al. OP0130 Composite of Relevant Endpoints in Sjogren's Syndrome (CRESS): A Comprehensive Tool for Clinical Trials. Annals of the Rheumatic Diseases 2021;80:74-75.

¹⁸ Griffiths N, et al. Content Validity of Sjögren's Syndrome Symptom Diary and Functional Assessment of Chronic Illness Therapy-Fatigue in Patients with Sjögren's. Rheumatol Ther. 2022 Dec;9(6):1559-1574. doi: 10.1007/s40744-022-00489-y.

¹⁹ Ling LE., et al. M281, an anti‐fcrn antibody: Pharmacodynamics, pharmacokinetics, and safety across the full range of IGG reduction in a first‐in‐human study. Clinical Pharmacology & Therapeutics., 2018;105;4:1031-1039. https://doi.org/10.1002/cpt.1276.

²⁰ ClinicalTrials.gov Identifier: NCT04951622. Available at: https://clinicaltrials.gov/ct2/show/NCT04951622. Last accessed: November 2024.

²¹ ClinicalTrials.gov. NCT03842189. Available at: https://clinicaltrials.gov/ct2/show/NCT03842189. Last accessed: November 2024

²² ClinicalTrials.gov Identifier: NCT05327114. Available at: https://www.clinicaltrials.gov/study/NCT05327114. Last accessed: November 2024

²³ ClinicalTrials.gov Identifier: NCT04119050. Available at: https://clinicaltrials.gov/study/NCT04119050. Last accessed: November 2024.

²⁴ ClinicalTrials.gov Identifier: NCT05379634. Available at: https://clinicaltrials.gov/study/NCT05379634. Last accessed: November 2024.

²⁵ ClinicalTrials.gov Identifier: NCT05912517. Available at: https://www.clinicaltrials.gov/study/NCT05912517. Last accessed: November 2024

²⁶ ClinicalTrials.gov Identifier: NCT06028438. Available at: https://clinicaltrials.gov/study/NCT06028438. Last accessed: November 2024.

²⁷ ClinicalTrials.gov Identifier: NCT04968912. Available at: https://clinicaltrials.gov/study/NCT04968912. Last accessed: November 2024.

²⁸ ClinicalTrials.gov Identifier: NCT04882878. Available at: https://clinicaltrials.gov/study/NCT04882878. Last accessed: November 2024.

²⁹ Roy S, Nanovskaya T, Patrikeeva S, et al. M281, an anti-FcRn antibody, inhibits IgG transfer in a human ex vivo placental perfusion model. Am J Obstet Gynecol. 2019;220(5):498 e491-498 e499.

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