Efgartigimod shows signals of benefit in Sjögren’s disease clinical trial
Small Phase 2 study found higher response rates than with a placebo
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Efgartigimod, a therapy approved for certain autoimmune diseases, led to higher response rates and greater reductions in certain immune markers than a placebo in adults with Sjögren’s disease, according to final data from a small proof-of-concept clinical trial.
Because the Phase 2 study, called RHO (NCT05817669), was not powered to detect statistically significant differences between the efgartigimod and placebo groups, a larger Phase 3 trial, called UNITY (NCT06684847), is currently underway to further test the therapy’s safety and efficacy.
While the Phase 2 study tested into-the-vein, or intravenous, efgartigimod (sold as Vyvgart), the Phase 3 trial is testing an under-the-skin, or subcutaneous, formulation (sold as Vyvgart Hytrulo). Neither formulation is approved for Sjögren’s disease.
Sjögren’s lacks approved disease-modifying treatments
RHO’s results were described in the study, “Efgartigimod in Sjögren’s disease: a phase 2, randomised, placebo-controlled, parallel-group, double-blinded, proof-of-concept study (RHO),” published in Annals of the Rheumatic Diseases.
Sjögren’s is an autoimmune disorder in which the immune system mistakenly attacks healthy tissues, particularly moisture-producing glands, such as the salivary and tear glands. The disease most commonly causes dry mouth and dry eyes, but can also result in symptoms affecting the joints, blood, lungs, kidneys, skin, and nervous system.
At present, no body-wide, disease-modifying therapies are approved for Sjögren’s, and current treatments largely focus on symptom relief.
“Despite a significant disease burden, no systemic [body-wide], disease-modifying treatments are approved for SjD [Sjögren’s disease],” the researchers wrote, and while certain immunosuppressive treatments are “used off-label for specific organ manifestations, current therapies focus primarily on individual symptom relief.”
Argenx’s efgartigimod is designed to block the neonatal Fc receptor (FcRn), a protein that helps stabilize IgG antibodies in the bloodstream. The therapy therefore promotes the breakdown of IgG antibodies, including some of the self-reactive antibodies thought to contribute to Sjögren’s. Efgartigimod is approved for certain adults with generalized myasthenia gravis, another autoimmune disease driven by self-targeting antibodies.
Small trial tested IV efgartigimod against a placebo
In the RHO study, 34 adults with at least moderate Sjögren’s disease activity were recruited across 12 sites in Belgium, Hungary, and Poland. They were randomly assigned to receive either efgartigimod at 10 mg/kg (23 patients) or a placebo (11 patients) once weekly for 24 weeks, or about six months.
One participant in the efgartigimod group and two participants in the placebo group “were excluded from the efficacy analysis due to the use of prohibited medications at screening,” the researchers wrote.
No formal statistical hypothesis was tested, meaning the trial was designed to look for signals of benefit rather than to definitively prove efficacy.
The study’s main goal was to assess the proportion of patients who responded on at least three of the five items in the Composite of Relevant Endpoints for Sjögren’s Syndrome (CRESS) after six months. These items measured systemic disease activity, patient-reported symptoms, tear gland function, salivary gland function, and blood levels of total IgG or rheumatoid factor.
Systemic disease activity was assessed with the Clinical EULAR Sjögren’s Syndrome Disease Activity Index. IgG is an antibody class that includes some antibodies thought to play a role in Sjögren’s, and rheumatoid factor is a self-reactive antibody associated with Sjögren’s and other autoimmune diseases.
Results showed that more patients given efgartigimod met that CRESS-based outcome than those given the placebo (45.5% vs. 11.1%). Efgartigimod had numerically better results than the placebo on four of the five CRESS components, with a greater proportion of patients on the therapy showing low disease activity (59.1% vs. 33.3%), improved tear gland function (27.3% vs. 11.1%), better salivary gland function (36.4% vs. 22.2%), and a reduction in certain antibodies, based on total IgG or rheumatoid factor (86.4% vs. 11.1%).
A comparable proportion of patients in both groups, about one-third, showed a response in the remaining component, patient-reported symptoms.
Trial also showed drops in IgG and rheumatoid factor
Response rates based on the candidate Sjögren’s Tool for Assessing Response also favored efgartigimod, with more efgartigimod-treated patients classified as responders relative to those on the placebo (54.5% vs. 33.3%).
Efgartigimod led to rapid reductions in total IgG levels in the blood, with maximum effects seen after one month. By week 24, IgG levels were reduced by a median of 62.5% with the therapy, while almost no change was seen with the placebo (0.8%). Blood rheumatoid factor levels also fell more with efgartigimod, by a median of 26.6% vs. 5.3% with placebo.
Treatment-emergent adverse events were reported in 87% of efgartigimod-treated patients and 63.6% of those given the placebo. All were mild or moderate in severity. Commonly reported adverse events included headache, common cold, upper respiratory tract infection, urinary tract infection, and influenza.
Because efgartigimod lowers IgG antibodies, which help fight infections, infections were tracked as adverse events of special interest. These occurred in 65.2% of efgartigimod-treated patients and 45.5% of those on the placebo. All infections were nonserious. No deaths occurred during the study.
The researchers noted that the study’s small size was a key limitation, especially because only nine participants in the placebo group were included in the efficacy analysis. Still, “data from the RHO study support proof-of-concept for efgartigimod in SjD [Sjögren’s disease],” the researchers wrote.
