Phase 2 Trial Results for Sjögren’s Syndrome & SLE Presented in 2nd Plenary Session at ACR Convergence 2022

PHILADELPHIA—At the second Plenary Session of ACR Convergence on Sunday, Nov. 13, speakers shared compelling efficacy and safety results from two phase 2 trials: remibrutinib for Sjögren’s syndrome and deucravacitinib for moderate to severe systemic lupus erythematosus.

Remibrutinib in Phase 2 Sjögren’s Syndrome Trial

Thomas Dörner, MD

Thomas Dörner, MD, a professor of rheumatology and clinical immunology for innovative therapies at Charite University Hospital Berlin and DRFZ Berlin, presented promising but mixed phase 2 results of remibrutinib, an oral inhibitor of Bruton’s tyrosine kinase (BTK), in Sjögren’s syndrome.¹

Dr. Dörner explained that even though the predominant cells infiltrating the exocrine glands in Sjögren’s syndrome are CD4-positive T cells, the syndrome is considered a B cell driven autoimmune disease resulting from abnormal response to autoantigens. Currently, no systemic oral therapies for the treatment of Sjögren’s syndrome have been approved by the U.S. Food & Drug Administration (FDA) to reduce the mouth and eye dryness, fatigue and joint pain associated with the condition, and the disease is often difficult to adequately treat.²

BTK plays a critical role in B cell receptor signaling, influencing B cell proliferation and differentiation. It also affects proinflammatory signaling through immunoglobulin Fc receptors, such as those in mast cells and macrophages. Various BTK kinase inhibitors are used to treat B cell malignancies, but agents currently approved for malignancy have significant off-target effects on other kinases. These cause side effects that have limited their use in other disease settings; these adverse side effects include platelet activation, which can cause stroke, and other cardiovascular effects.^3,4

Remibrutinib (LOU064) is a novel BTK inhibitor with different binding characteristics and greater selectivity for BTK than previously developed drugs.³ Scientists have been exploring the drug in various autoimmune, allergic and inflammatory diseases, such as multiple sclerosis and chronic spontaneous urticaria, which recently completed a successful phase 2 trial.^5,6

LOUiSSe Trial Results

The LOUiSSe trial was a double-blind, randomized, placebo-controlled phase 2 trial to evaluate efficacy and safety in patients with moderate to severe Sjögren’s syndrome.¹ All patients met ACR classification criteria for Sjögren’s syndrome and had a score of 5 or higher on the EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI), a clinician-reported outcome that includes 12 different domains of disease activity.^1,7

All participants also had an initial score of 5 or higher on the EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI). On this questionnaire, patients scale their dryness, fatigue and joint/muscle pain from 0–10 over the previous two weeks, and the mean of the three domains is the ESSPRI score.⁷