Promising Phase 2 Results for Efgartigimod alfa-fcab in Adults with Primary Sjögren’s Disease

BARCELONA—During EULAR 2025, Isabelle Peene, MD, PhD, Ghent University Hospital and Unit Molecular Immunology and Inflammation, Belgium, reported positive results from a phase 2 study of intravenous (IV) efgartigimod alfa-fcab (Vyvgart) for patients with primary Sjögren’s disease.¹

Primary Sjögren’s disease is a chronic, systemic, autoimmune disease characterized by lymphocytic infiltration and progressive, immune-mediated dysfunction of the exocrine glands. B cell activation plays a central role in disease development, resulting in the production of immunoglobulin (Ig) G autoantibodies—especially those that target Sjögren’s disease-related antigens A/Ro and B/La ribonuclear complexes—and rheumatoid factor, as well as elevated levels of serum IgG.² Currently, no systemic disease-modifying medications are approved by the U.S. Food & Drug Administration (FDA) to treat primary Sjögren’s disease.

The Agent

Efgartigimod alfa-fcab is a neonatal Fc receptor (FcRn) blocker, a human IgG1 antibody fragment that binds to the neonatal Fc receptor, resulting in the reduction of circulating IgG.

On Dec. 17, 2021, the FDA approved IV efgartigimod alfa-fcab as an orphan drug for the treatment of generalized myasthenia gravis in adults who are anti-acetylcholine receptor (AChR) antibody positive.³ Subsequently, the FDA approved efgartigimod alfa-fcab and efgartigimod alfa combined with hyaluronidase-qvfc (Vyvgart Hytrulo) for in-home use.^4,5 Efgartigimod alfa and hyaluronidase-qvfc, an endoglycosidase, is also FDA approved for the treatment of generalized myasthenia gravis and chronic inflammatory demyelinating polyneuropathy.⁶

In June, the FDA granted efgartigimod a fast-track designation for the treatment of primary Sjögren’s disease.⁷ Additionally, Argenx, the manufacturer of efgartigimod, announced results from another phase 2 study of efgartigimod alfa-fcab and efgartigimod alfa combined with hyaluronidase-qvFC in idiopathic inflammatory myopathies (i.e., myositis).⁷

The Findings

The study from Peene et al. was a phase 2, proof-of-concept, clinical trial of IV efgartigimod alfa-fcab in patients with primary Sjögren’s disease. Its results demonstrated significant improvements in systemic disease activity and patient symptoms, as well as a favorable safety profile.¹

At week 24, 45.5% of patients receiving efgartigimod alfa-fcab achieved improved outcomes on the Composite of Relevant Endpoints for Sjögren’s Syndrome (CRESS) scale, the study’s primary end point, which includes systemic disease activity and salivary and tear gland function. For comparison, 11.1% of patients treated with placebo achieved improved outcomes on CRESS.

Patients treated with efgartigimod alfa-fcab experienced rapid biomarker responses, with a sustained reduction in IgG (approximately 60%) beginning at week 4. This response indicates that targeting FcRn and reducing IgGs has a meaningful impact on disease.

Additionally, a median change in the Clinical European League Against Rheumatism Sjögren’s Syndrome Disease Activity Index (clinESSDAI) total score of -7 occurred in patients treated with efgartigimod alfa-fcab, compared with a total score of -4 in patients treated with placebo. The clinESSDAI is used to assess patients with primary Sjögren’s disease when evaluating disease activity independent of B-cell biomarkers or when biological data is not available. The total ClinESSDAI score is calculated by adding the scores from 11 organ-related domains—each with a potential score ranging from 0 to 3—and then weighting them with corresponding, domain-specific measures.

Secondary End Points

The cSTAR composite of five disease measures was a key secondary end point. In the study, patients treated with efgartigimod alfa-fcab had a 54.5% cSTAR response rate compared with a 33.3% response rate in patients treated with placebo. cSTAR is tool for assessing response in Sjögren’s disease used in clinical trials. It is a composite responder index that evaluates treatment effectiveness.

Additionally, patients treated with efgartigimod alfa-fcab had noticeable decreases in the disease-associated antibodies anti-Ro52 (-57% vs. +13%) and rheumatoid factor (-26.6% vs. -5.3%) compared with those who received placebo. Patients treated with efgartigimod alfa-fcab also had a greater decrease in C1Q immune complexes (-4.5 vs. -0.06 mc eq/mL) than those treated with placebo.

No new safety signals were identified.

Conclusion

This study served as proof of concept for using efgartigimod alfa-fcab for the treatment of patients with primary Sjögren’s disease.

A phase 3 trial, the UNITY trial (NCT06684847) is currently underway to assess the safety and efficacy of efgartigimod alfa-fcab in patients with primary Sjögren’s disease and a clinESSDAI score of 6 or greater, which indicates moderate to severe systemic disease activity.⁸

Michele B. Kaufman, PharmD, BCGP, is a freelance medical writer based in New York City and a pharmacist at New York Presbyterian Lower Manhattan Hospital.

References

1. Peene I, Mariette X, Elewaut D, et al. Treatment of Sjögren’s disease by blocking FcRn: clinical and translational data from Rho, a phase 2 randomized, placebo controlled, double-blind, proof-of-concept study with efgartigimod [OP0041]. Ann Rheum Dis. 2025 Jun; 84(suppl 1):37.
2. Baer AN. Diagnosis and classification of Sjögren’s disease. UpToDate. 2025 May 5.
3. Argenx BV biologics license application: General advice letter. U.S. Food & Drug Administration. 2021 Dec 17.
4. Argenx announces FDA approval of Vyvgart hytrulo prefilled syringe for self-injection in generalized myasthenia gravis and chronic inflammatory demyelinating polyneuropathy [news release]. Argenx. 2025 Apr 10.
5. Supplemental approval letter: Vyvgart (efgartigimod alfa-fcab) and Vyvgart Hytrulo (efgartigimod alfa and hyaluronidase-qvfc). U.S. Food & Drug Administration. 2024 Aug 8.
6. Argenx announces FDA approval of Vyvgart Hytrulo prefilled syringe for self-injection in generalized myasthenia gravis and chronic inflammatory demyelinating polyneuropathy [news release]. Argenx. 2025 Apr 10.
7. Argenx presents new efgartigimod data at EULAR 2025 highlighting positive phase 2 proof-of-concept results in myositis and Sjogren’s disease [news release]. Argenx. 2025 Jun 11.
8. Argenx. A study of the efficacy and safety of efgartigimod in patients with primary Sjögren’s syndrome (NCT06684847). ClinicalTrials.gov. 2025 Jun 13.