Can Johnson & Johnson’s nipocalimab redefine autoimmune treatment by targeting Sjögren’s disease at its root?

Johnson & Johnson (NYSE: JNJ) has released peer-reviewed clinical data from its Phase 2 DAHLIAS study, published in The Lancet, confirming that nipocalimab—its first-in-class investigational FcRn-blocking monoclonal antibody—significantly reduced disease activity in patients with moderate-to-severe Sjögren’s disease. This pivotal readout marks one of the most promising advances to date in the treatment of this historically neglected autoimmune condition. With both Breakthrough Therapy Designation and Fast Track status from the U.S. Food and Drug Administration, the momentum behind nipocalimab is now building toward Phase 3 validation.

The DAHLIAS trial not only met its primary endpoint but also demonstrated meaningful symptom relief, improved biological markers, and a favorable safety profile. These outcomes add substantial weight to Johnson & Johnson’s broader strategy of expanding nipocalimab’s indications across autoantibody-mediated diseases. The American pharmaceutical and healthcare giant has already begun enrolling patients in its Phase 3 DAFFODIL study for Sjögren’s disease, which could potentially lead to the first approved systemic treatment for the condition.

What do the Phase 2 DAHLIAS results suggest about nipocalimab’s clinical value in Sjögren’s disease?

In the DAHLIAS study, 163 adults aged between 18 and 75 years with active, seropositive primary Sjögren’s disease were randomized into three treatment groups to receive either placebo or intravenous doses of nipocalimab at 5 mg/kg or 15 mg/kg every two weeks for 22 weeks. All patients continued on background standard-of-care therapies, as per protocol. The primary endpoint measured the change in ClinESSDAI score at Week 24. This composite index evaluates disease activity across 11 systemic domains such as glandular involvement, joint pain, constitutional symptoms, lymphadenopathy, renal and respiratory features, and hematological indicators.

Results showed a statistically significant improvement in ClinESSDAI scores in the high-dose 15 mg/kg group compared to placebo. This clinical benefit was further supported by biomarker reductions in rheumatoid factor levels, lower immune complex load, and decreases in systemic inflammatory markers. These changes are considered highly relevant to the autoantibody-driven pathology of Sjögren’s disease, which affects exocrine glands and leads to debilitating dryness, fatigue, and systemic complications.

More than double the number of patients in the high-dose nipocalimab arm showed improved salivary flow—defined as a 50 percent increase from baseline—compared to the placebo group (33 percent versus 16 percent). Subjective symptoms also trended in favor of nipocalimab, including reductions in fatigue, joint pain, and mucosal dryness in the mouth, eyes, and vaginal tissues. These are hallmark features that significantly impair quality of life and daily functioning.

How does the mechanism of action behind nipocalimab address the core pathogenesis of autoantibody-mediated diseases?

Nipocalimab is designed to selectively block the neonatal Fc receptor (FcRn), a key protein that extends the half-life of circulating immunoglobulin G antibodies. By inhibiting FcRn, nipocalimab accelerates the breakdown of pathogenic autoantibodies, thereby lowering IgG levels without broadly suppressing immune function. This differentiates it from corticosteroids and other immunosuppressants that compromise multiple arms of the immune system, increasing the risk of infection and long-term complications.

In commentary included in The Lancet, Dr. Ghaith Noaiseh, Associate Professor of Allergy, Clinical Immunology, and Rheumatology at The University of Kansas Medical Center, emphasized the promise of FcRn inhibition as a targeted therapy in systemic autoimmune diseases. He noted that nipocalimab’s ability to lower IgG autoantibody levels rapidly and reversibly aligns well with the underlying mechanisms of Sjögren’s disease. According to Dr. Noaiseh, these results suggest that nipocalimab may offer a much-needed disease-modifying option for patients who currently rely on symptomatic treatments alone.

What unmet needs does nipocalimab address in the current treatment landscape for Sjögren’s disease?

Sjögren’s disease is one of the most common but under-addressed autoimmune disorders, affecting an estimated four million people globally. Approximately 90 percent of patients are women. It is characterized by lymphocytic infiltration of exocrine glands, resulting in dryness of the eyes, mouth, and vaginal mucosa, as well as systemic manifestations including joint pain, fatigue, and organ involvement.

Despite the burden of the disease being comparable to rheumatoid arthritis or systemic lupus erythematosus, there are currently no systemic therapies approved by the U.S. Food and Drug Administration or other global regulatory authorities that target its underlying pathophysiology. Current treatment approaches focus on symptom management with artificial tears, saliva substitutes, and off-label immunomodulators. Many patients experience a progressive decline in quality of life, with studies suggesting that up to half of all patients are unable to continue full-time work due to fatigue and functional disability.

By targeting a central mechanism of disease progression, nipocalimab offers the possibility of a disease-modifying approach. Its safety profile, as observed in DAHLIAS, also avoids many of the risks associated with broader immune suppression.

What is the broader clinical and regulatory context for nipocalimab beyond Sjögren’s disease?

Nipocalimab is also being evaluated across three major categories of autoantibody-mediated conditions: rare diseases such as warm autoimmune hemolytic anemia, maternal–fetal conditions including hemolytic disease of the fetus and newborn (HDFN), and systemic autoimmune disorders like chronic inflammatory demyelinating polyneuropathy (CIDP).

Johnson & Johnson has already secured multiple regulatory designations for nipocalimab, including Fast Track and Orphan Drug status from the U.S. Food and Drug Administration. In November 2024, the therapy was granted Breakthrough Therapy Designation specifically for Sjögren’s disease. Priority Review status was awarded in late 2024 for its generalized myasthenia gravis indication under the brand name IMAAVY™, which is now approved in the United States, Brazil, and Japan. The therapy is also under regulatory review in several other countries for various indications.

Health authorities across Europe and the United States have acknowledged nipocalimab’s potential as a pipeline-in-a-product asset, capable of addressing both rare and common autoimmune diseases with limited treatment options. Johnson & Johnson’s legal manufacturer for IMAAVY is Janssen Biotech, Inc.

What is the outlook for Johnson & Johnson’s Phase 3 DAFFODIL trial and commercial strategy in immunology?

The DAFFODIL Phase 3 study is now actively enrolling patients to further evaluate nipocalimab in moderate-to-severe primary Sjögren’s disease. If successful, the data could support the first-ever regulatory filing for a targeted systemic treatment for this condition. Analysts expect topline data from DAFFODIL to emerge by late 2026 or early 2027, with potential for accelerated approval depending on the robustness of the efficacy and safety data.

From a commercial perspective, Johnson & Johnson is positioning nipocalimab not just as a single-indication therapy but as a foundational asset in its autoimmune and rare disease portfolio. Institutional interest remains high, especially given the drug’s potential across multiple indications and geographies. Many analysts see nipocalimab as a potential multi-billion-dollar franchise if approved for a broad spectrum of autoantibody-driven diseases.

Investor sentiment has been largely positive, with Johnson & Johnson’s stock (NYSE: JNJ) showing resilience amid broader healthcare sector volatility. The publication of DAHLIAS data in The Lancet has added further credibility to the clinical value proposition of nipocalimab and reinforced expectations that the drug will play a key role in the company’s medium-term pipeline growth strategy.

How are investors and analysts reacting to Johnson & Johnson’s autoimmune drug strategy in 2025?

Johnson & Johnson stock has traded in a relatively tight range over the past quarter, with modest gains reflecting positive investor sentiment around its late-stage pipeline assets, including nipocalimab. Institutional flows have remained stable, with several long-only funds maintaining their positions.

The publication of Phase 2 results in a high-impact journal like The Lancet has strengthened market confidence in the clinical rigor and future regulatory viability of nipocalimab. Analysts believe that the compound could help Johnson & Johnson offset biosimilar pressure on its older immunology products and support its ongoing efforts to lead in differentiated biologics.

Should DAFFODIL deliver strong data, Johnson & Johnson could become the first pharmaceutical company to commercialize a systemic treatment for Sjögren’s disease—a milestone that would also significantly shift competitive dynamics in autoimmune drug development.

What are the essential takeaways investors, clinicians, and patients should know right now about nipocalimab’s DAHLIAS Phase 2 results?

• Nipocalimab met the DAHLIAS Phase 2 primary endpoint with a statistically significant improvement in ClinESSDAI score at Week 24 for the 15 mg/kg every‑2‑weeks group versus placebo.
• Biomarker improvements accompanied clinical benefit, including reductions in rheumatoid factor, fewer circulating immune complexes, and lower systemic inflammatory markers that align with the drug’s mechanism of FcRn inhibition.
• Objective salivary flow showed meaningful gains, with about 33 percent of high‑dose patients achieving at least a 50 percent increase from baseline versus 16 percent for placebo, reflecting potential reversal of glandular dysfunction.
• The safety profile was tolerable and consistent with existing IMAAVY data in generalized myasthenia gravis; there were no new safety signals, no rise in serious infections, and no participants required intravenous immunoglobulin or rescue therapy during the 24‑week period.
• Regulatory momentum is favorable: nipocalimab has Breakthrough Therapy Designation and Fast Track status from the U.S. Food and Drug Administration for Sjögren’s disease, and the Phase 3 DAFFODIL study is actively enrolling.
• Commercially, Johnson & Johnson is positioning nipocalimab as a multi‑indication FcRn franchise; if DAFFODIL is positive, the drug could become the first approved systemic therapy for Sjögren’s disease and significantly expand Johnson & Johnson’s autoimmune pipeline value—investors will watch DAFFODIL readouts (expected by late 2026/early 2027) as the next major catalyst.