J&J Reports Positive Phase 2 Sjögren’s Results

Rare Daily Staff

Johnson & Johnson said patients treated with its experimental therapy nipocalimab demonstrated statistically significant and clinically meaningful improvement in its phase 3 DAHLIAS study in people with Sjögren’s disease.

The primary endpoint for the study was ClinESSDAIa score versus placebo at 24 weeks compared to baseline in adult patients living with Sjögren’s disease (SjD). 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), hematological, glandular, constitutional, lymphadenopathy and lymphoma]; a higher score indicates greater symptom severity.

Response was demonstrated as early as Week 4 and continued to increase throughout the 24-week treatment period compared with patients receiving placebo. These data represent the first positive results in SjD for nipocalimab. The study results were featured in a late-breaking presentation at the European Alliance of Associations for Rheumatology 2024 Congress.

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. SjD is characterized by autoantibody production, chronic inflammation, and lymphocytic infiltration of exocrine glandular systems. Most patients are affected by mucosal dryness (eyes, mouth, vagina), joint pain and fatigue. Extraglandular manifestations are common and may impact multiple organ systems, including joints, lungs, kidneys, and nervous system.

Patients with SjD have a high risk of developing numerous associated conditions, including up to 20 times higher risk of developing B-cell lymphomas when compared to the general population. SjD increases all-cause mortality risk by approximately 50 percent more than the general population, and high activity in more than one organ/disease domain increases mortality risk by up to five-fold. It is usually associated with impaired quality of life and functional capacity.

Nipocalimab is an experimental monoclonal antibody, purposefully designed to bind with high affinity to block FcRn and reduce levels of circulating immunoglobulin G (IgG) antibodies, while preserving immune function without causing broad immunosuppression. This includes autoantibodies and alloantibodies that underlie multiple conditions across three key segments in the autoantibody space including rare autoantibody diseases, maternal fetal diseases mediated by maternal alloantibodies, and prevalent rheumatology.

The U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) have granted several key designations to nipocalimab including Fast Track designation in HDFN and warm autoimmune hemolytic anemia (wAIHA), gMG, and fetal neonatal alloimmune thrombocytopenia. It has Orphan Drug designation in wAIHA, HDFN, gMG, chronic inflammatory demyelinating polyneuropathy (CIDP), and FNAIT. And it has Breakthrough Therapy designation for HDFN. The European Medicines Agency granted nipocalimab Orphan Medicinal Product designation for HDFN.

In addition to achieving the primary endpoint, the nipocalimab 15 mg/kg treatment group demonstrated clinically meaningful improvements in secondary endpoints at Week 24 including multiple organ assessments, physician assessments, and composite tools for clinical trial endpoints.

“These data establish proof of concept for nipocalimab in Sjögren’s disease and support further clinical development, which is welcome news for the approximately four million people worldwide living with this chronic, debilitating disease,” said Jacques-Eric Gottenberg, of the National Centre for Rare Systemic Autoimmune Diseases and study investigator. “SjD patients need approved advanced therapies that can help address the serious health consequences of the disease, and I am encouraged by these results and the positive impact on disease measures that are clinically meaningful.”