Efgartigimod Sustains Sjögren's Disease Control Through 48 Weeks in RHO+ OLE

Intravenous efgartigimod demonstrated maintained disease control and a consistent safety profile through 48 weeks of follow-up in the RHO+ open-label extension (OLE) study of adults with Sjögren's disease, with most responders able to transition to biweekly dosing without loss of efficacy, according to data presented at EULAR 2026.¹

Sjögren's disease is a chronic, progressive systemic autoimmune condition characterized by immune-mediated exocrine gland dysfunction, extraglandular organ involvement, and the presence of IgG autoantibodies against Ro52, Ro60, and La antigens. No disease-modifying therapies are currently approved for Sjögren's disease, leaving a substantial unmet need for patients with moderate-to-severe systemic involvement.

Efgartigimod works by blocking the neonatal Fc receptor (FcRn), selectively reducing circulating IgG autoantibodies without broadly suppressing the immune system or affecting other immunoglobulin classes.²

Isabelle Peene, MD, PhD, of Ghent University Hospital, who presented the data, noted that the consistency of response across both the antecedent RHO study and the RHO+ OLE strengthens confidence in the mechanistic rationale for FcRn targeting in Sjögren's disease.

"The treatment effect stays consistent throughout both studies," Peene said, adding that the biweekly dosing maintenance seen in most responders at week 48 represents a meaningful signal of stable disease control over time.

RHO+ OLE Design, Efficacy Outcomes, and CRESS Response Rates

The RHO+ OLE enrolled 24 participants who rolled over from the phase 2 RHO study after completing its 24-week treatment period.¹ Of these, 17 participants had previously received efgartigimod IV in RHO and formed the EFG-EFG arm; 7 who had received placebo crossed over to efgartigimod and formed the PBO-EFG arm.

Participants received efgartigimod IV for up to 48 weeks during the OLE. Responders in the antecedent RHO study, defined as those achieving a reduction in clinESSDAI score of at least 3 points from baseline or reclassification from moderate to mild disease activity (clinESSDAI <5), were transitioned to biweekly dosing in RHO+, with reversion to weekly dosing if disease worsening was observed.

Overall, 17 participants had week 48 assessments available for efficacy analysis. At week 48, 9 of 13 EFG-EFG participants and 3 of 4 PBO-EFG participants were receiving biweekly dosing, supporting the durability of response with extended treatment.¹

Efficacy outcomes were evaluated using the Composite of Relevant Endpoints for Sjögren's Syndrome (CRESS), which requires response on ≥ 3 of 5 items. In a post-hoc analysis using the antecedent RHO study baseline as the reference point, CRESS response at week 48 was achieved by 38% of EFG-EFG participants (5 of 13) and 75% of PBO-EFG participants (3 of 4).¹ In the antecedent RHO study, 45% of efgartigimod-treated participants had been CRESS responders compared with 11% in the placebo group.

Disease activity as measured by clinESSDAI showed further improvement from OLE baseline to week 48, with median changes of -0.5 in the EFG-EFG arm and -4.0 in the PBO-EFG arm. At week 48, 7 EFG-EFG participants and 3 PBO-EFG participants achieved low disease activity, defined as clinESSDAI < 5. ESSDAI total scores also showed further reductions from OLE baseline at week 48, with decreases of -1.5 and -4.0 in the EFG-EFG and PBO-EFG arms respectively.

Peene noted that patient-reported symptom burden, as measured by ESSPRI, remains a difficult endpoint to move in Sjögren's disease trials broadly, and that the current OLE dataset is too small to draw meaningful conclusions on this domain.

Safety Profile and the Path Toward Phase 3 UNITY Trial Results

Safety data from the RHO+ OLE were consistent with findings from the antecedent RHO study and with efgartigimod's established safety profile across its approved indications.¹ Treatment-emergent adverse events (TEAEs) occurred in 87.5% of participants overall, with rates similar between the EFG-EFG arm (88.2%) and PBO-EFG arm (85.7%), and most events were mild to moderate in severity.

Two serious adverse events were reported in the PBO-EFG arm, a moderate infusion-related reaction and a severe hypersensitivity event, both considered treatment-related and both leading to discontinuation. Both resolved within one hour with treatment and neither required hospitalization. No serious adverse events were reported in the EFG-EFG arm, and no serious infections were reported in either arm.

The phase 3 UNITY trial is currently ongoing to assess the efficacy and safety of subcutaneously administered efgartigimod PH20 in patients with moderate-to-severe Sjögren's disease, with topline results expected in the second half of 2027. UNITY is a randomized, double-blind, placebo-controlled multicenter study with an open-label extension. Peene noted that definitive conclusions on symptom response and broader clinical endpoints will require the larger, adequately powered Phase 3 dataset UNITY will provide.¹

References

1. Peene I, Verstappen GM, Arends S, et al. Long-term efficacy and safety of efgartigimod in Sjögren's disease: findings from the RHO+ open-label extension study. Presented at: EULAR 2026; June 3-6, 2026; London, UK. Abstract OP0130.

2. Goetze RG, Harder MN, Jakobsen MA, et al. Efgartigimod for autoimmune diseases — FcRn inhibition and IgG reduction. N Engl J Med. 2023;388(24):2232-2245. doi:10.1056/NEJMra2213755

3. argenx. argenx presents new efgartigimod data showing long-term sustained patient benefit in myositis and Sjögren's disease at EULAR 2026. Press release. June 3, 2026. https://argenx.com/news/2026/press-release-3305765