Phase II DAHLIAS Trial Results Lead to Fast Track Designation for Nipocalimab for Sjögren’s Disease

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Based on data from the Phase II DAHLIAS (NCT04968912) trial, the FDA has granted Fast Track designation (FTD) to nipocalimab for the treatment of moderate-to-severe Sjögren’s disease.^1,2 The FTD, which is the first ever granted to a treatment for Sjögren’s disease, will help to advance the development of the investigational therapy, which if approved, would be the first targeted therapy indicated for the autoantibody-driven disease.

“This marks an additional important step forward in our efforts to bring meaningful advancements to people living with Sjögren’s disease, a serious and debilitating condition,” Katie Abouzahr, MD, vice president, Autoantibody Portfolio and Maternal Fetal Disease Area Leader, Johnson & Johnson Innovative Medicine, said in a press release. “We look forward to continuing to work closely with the FDA to advance the clinical development of nipocalimab and potentially provide a much-needed treatment option for this community.”¹

Nipocalimab is a high-affinity, fully human, aglycosylated, effectorless, monoclonal antibody, acting as an anti-neonatal Fc receptor (FcRn). In addition to the FTD for Sjögren’s disease, the novel therapy has previously been granted FTD for hemolytic disease of the fetus and newborn (HDFN), warm autoimmune hemolytic anemia, generalized myasthenia gravis (gMG), and fetal neonatal alloimmune thrombocytopenia (FNAIT). Nipocalimab has also been granted Orphan drug designation for warm autoimmune hemolytic anemia, HDFN, gMG, chronic inflammatory demyelinating polyneuropathy, and FNAIT. Additionally, it has been awarded FDA Breakthrough Therapy designation for HDFN and for Sjögren’s disease, with Priority Review status granted for gMG late last year.¹

Trial Design

The multicenter, randomized, placebo-controlled double-blind, DAHLIAS trial analyzed the efficacy of nipocalimab in patients with primary Sjögren’s disease. The dose-ranging study included 163 patients aged 18-75 years with moderately-to-severely active primary Sjögren’s disease who are seropositive for anti-Ro60 and/or anti-Ro52 IgG antibodies.

Patients were randomly assigned in a 1:1:1 ratio to receive either intravenous nipocalimab at a dose of 5 mg/kg, 15 mg/kg, or placebo every two weeks for 22 weeks, as well as protocol-permitted background standard of care. The trial’s primary endpoint was change from baseline in the Clinical European League Against Rheumatism Sjögren’s Syndrome Disease Activity Index (ClinESSDAI) score at 24 weeks.

The results showed improvements across key measures of disease activity in patients administered nipocalimab. These patients experienced a significant decrease in immunoglobulin G (IgG) of more than 77% with the 15 mg/kg dose level administered every two weeks. Investigators said this reinforces the mechanism of action of nipocalimab through interaction with the neonatal Fc receptor.³

Patients administered the 15 mg/kg dose of nipocalimab experienced a significant improvement in the ClinESSDAI score at 24 weeks, showing a greater than 70% relative average improvement in systemic disease activity, which met the trial’s primary endpoint. Nipocalimab also achieved the trial’s key secondary endpoints, including reduced disease activity both systemically and in multiple organ systems, and in improved physician assessments and composite Sjögren’s disease assessments.

Compared with placebo, there were also numerical improvements reported in symptoms identified as most important to participants, which included mouth dryness, eye dryness, vaginal dryness, fatigue, and joint pain.

“The observed reduction in IgG and pivotal autoantibodies, particularly the 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,” Ghaith Noaiseh, MD, associate professor, Allergy, Clinical Immunology, and Rheumatology, The University of Kansas Medical Center, said in a press release. “I am also encouraged by the observed trend in many patient-reported measures as they are most important to patients. I look forward to future research to confirm these observations.”³

References

1. Nipocalimab, the first and only investigational treatment to be granted U.S. FDA Breakthrough Therapy designation for the treatment of adults with moderate-to-severe Sjögren’s disease, has now received Fast Track designation. News release. Johnson & Johnson. March 18, 2025. Accessed March 18, 2025. https://www.jnj.com/media-center/press-releases/nipocalimab-the-first-and-only-investigational-treatment-to-be-granted-u-s-fda-breakthrough-therapy-designation-for-the-treatment-of-adults-with-moderate-to-severe-sjogrens-disease-has-now-received-fast-track-designation

2. A Study of Nipocalimab in Adults With Primary Sjogren's Syndrome (pSS). ClinicalTrials.gov. Updated March 4, 2025. Accessed March 18, 2025. https://clinicaltrials.gov/study/NCT04968912

3. Nipocalimab demonstrates significant clinical improvement in disease activity and IgG reduction in Phase 2 Sjögren’s disease study. News release. Johnson & Johnson. November 14, 2024. Accessed March 18, 2025. https://www.jnj.com/media-center/press-releases/nipocalimab-demonstrates-significant-clinical-improvement-in-disease-activity-and-igg-reduction-in-phase-2-sjogrens-disease-study