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Advancements and Challenges in Sjogren’s Syndrome Treatment: EULAR 2024 Insights

Emerging landscape of Sjogren’s Syndrome: Interleukin inhibitors, CD40 inhibitors, FcRn inhibitors

The therapeutic management of Sjogren’s syndrome has not changed substantially in recent decades and is still based on symptomatic treatment of sicca symptomatology and broad-spectrum immunosuppression for systemic disease, with insufficient information on the differential efficacy and safety of the therapeutic options available. Treatment decisions remain challenging in clinical practice, without a specific therapeutic target beyond the relief of symptoms as the most important goal. Therefore, there is a growing interest in the proposal of clinical guidelines by national scientific societies. 

POS0373: Zura Bio’s Tibulizumab (LY3090106; ZB-106), a dual blocker of IL-17A and BAFF, was well-tolerated and that the combined neutralization of IL-17A and BAFF disrupts two key pathways involved in disease pathogenesis.

POS0375: Lusvertikimab (S95011; OSE-127), an IL-7 receptor monoclonal antibody, did not demonstrate effectiveness in treating pSS over 13 weeks. The mean ESSDAI and ESSPRI scores were similar between S95011 and placebo groups, indicating no significant improvement in disease activity.

LBA0010: In Phase II study (DAHLIAS; NCT04968912), Johnson & Johnson’s nipocalimab (FcRn inhibitor) showed efficacy in primary Sjogren’s syndrome, meeting primary endpoints at Week 24. It significantly improved clinical disease activity compared to placebo, with similar improvements in most secondary/exploratory endpoints in the 15 mg/kg group.

OP0008: Novartis' iscalimab, also known as CFZ533 (CD40 inhibitor [Blocking, non-depleting, anti-CD40 monoclonal antibody]) demonstrated efficacy in reducing disease activity in Sjogren’s syndrome patients. Switching from placebo to iscalimab showed improvements in ESSDAI and ESSPRI scores, with a consistent safety profile across different dose groups.

Efficacy and Safety of Drugs in Sjogren’s Syndrome

Abstract Number

Title

Results

POS0373

Innovative IL-17A/BAFF Dual Blocker: Phase Insights for Sjogren’s Syndrome

  • BAFF and IL-17A concentrations reached a plateau, indicating maximum target engagement during treatment with tibulizumab.

  • Tibulizumab reduced levels of exploratory biomarkers such as total B cell counts and CXCL1.

  • PK/PD modeling estimated a subcutaneous bioavailability of approximately 62.9% for tibulizumab, with a time to reach maximum concentration (tmax) between 5 to 8 days post-dose.

  • Only one participant treated with tibulizumab (30mg every 4 weeks) developed treatment emergent anti-drug antibodies (ADA) during the study.

POS0375

Comprehensive Assessment of S95011 (OSE-127, Lusvertikimab) - A Monoclonal Antibody Targeting IL-7 Receptor for Sjögren’s Syndrome Treatment

  • Mean ESSDAI was 11.5 (3.7) and 13.1 (7.2) and mean ESSPRI was 7.1 (1.6) and 6.9 (1.7) for S95011 and placebo groups, respectively.

  • The change in ESSDAI from baseline to week 13 was similar in both groups: -3.9 (4.4) for the placebo group and -3.9 (6.5) for the S95011 group.

  • S95011 did not show effectiveness in treating patients with pSS, indicating that blocking the IL-7 pathway for 13 weeks may not be enough to influence the progression of the disease. However, the safety of S95011 was considered acceptable.

LBA0010

Phase II DAHLIAS Study: Evaluating Efficacy and Safety of Nipocalimab in Primary Sjogren’s Disease

Primary endpoints were met in Week 24:

  • Total Clinical European League Against Rheumatism Sjögren’s Syndrome Disease Activity: Index (clinESSDAI) ≥6 was -6.40 in the nipocalimab 15 mg/kg arm, -4.08 in the nipocalimab 5 mg/kg arm vs. -3.74 in placebo arm

Similar improvements in the 15 mg/kg nipocalimab group vs. placebo were observed in most secondary/exploratory endpoints.

OP0008

48-Week Results of Phase IIb Trial on Iscalimab: Evaluating Safety and Efficacy in Sjögren’s Disease Patients

Efficacy

PBO-treated patients switched to iscalimab 600 mg (C1) and 300 mg (C2)

ESSDAI LS mean change from baseline at Week 24 in C1

  • Iscalimab 150 mg: -7.6

  • Iscalimab 300 mg: -5.7

  • Iscalimab 600 mg: -7.9

  • PBO-treated-switched to Iscalimab 600 mg: -6.7

In C2, improvements in ESSPRI were observed in both PBO-iscalimab 300 mg and iscalimab 600 mg (∆: -2.14 and -2.29, respectively) at Week 48 and were consistent with C1

Safety

  • No dose-dependent increase in adverse events (AEs) or serious AEs (SAEs) in C1.

  • SAE rates: 4.9% (PBO), 11.4% (iscalimab 150 mg), 14.3% (iscalimab 300 mg), 11.4% (iscalimab 600 mg) in C1.

  • Comparable SAE rates between PBO and iscalimab 300 mg/600 mg (11.4% and 12.0%, respectively) in C2.

KOL Insight

“From the Danbio Registry showed that patients who used the system were mainly 40-80 years of age, on biologics and had lower HAQ score. Disease duration and diagnosis had no impact.” 

  •  Rheumatologist, UK

“Phase II RCT Iscalimumab, anti-CD40mAb in two cohorts (1=High systemic activity; 2=High symptom burden but low systemic) showed sustained improvement in ESSDAI & ESSPRI at 48 weeks in ISC-ISC group, as well as those switched at 24 weeks from PBO-ISC.” 

  • Rheumatologist, UK

Conclusion: The growth of the Sjogren’s syndrome disease market is expected to be mainly driven by the growing prevalence, research and development, upcoming approvals and launches, identification of potential biomarkers, etc. 

The current treatment landscape primarily revolves around symptomatic management, including artificial tears for dry eyes, saliva substitutes for dry mouth, and immunosuppressive agents like hydroxychloroquine or methotrexate for systemic symptoms. However, there's a significant unmet need for therapies that target the underlying immune dysfunction. 

Emerging drugs like tibulizumab, nipocalimab, and iscalimab offer potential breakthroughs by targeting specific pathways involved in Sjogren’s syndrome, which could lead to more targeted and effective treatments, potentially altering the standard of care. Iscalimab is expected to garner the highest market size with a revenue of ~USD 2,040 million, respectively, by 2034 in the 7MM.

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Executive Summary

The current therapeutic approach to Sjogren’s syndrome focuses on symptomatic relief and broad immunosuppression due to a lack of specific targets. Emerging drugs like tibulizumab and nipocalimab offer promise but require further efficacy validation, while iscalimab shows potential for improving disease activity, highlighting a need for targeted therapies and updated clinical guidelines.

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