Dazodalibep reduces Sjögren’s syndrome-related symptoms

Treatment with dazodalibep, a novel nonantibody fusion protein that acts as an antagonist of CD40 ligand, significantly reduced symptom burden in adults with Sjögren’s syndrome, according to the ALISS trial presented at EULAR 2023.

“Sjögren’s is a systemic autoimmune disease associated with reduced health-related quality of life, generally driven by the cardinal symptoms of the disease, such as dryness, pain, and fatigue … and the severity of these symptoms were assessed using ESSPRI*,” said Dr Chiara Baldini from the Department of Clinical and Experimental Medicine, Rheumatology Unit, at the University of Pisa, Pisa, Italy.

“There are currently no disease-modifying FDA-approved treatments for Sjögren’s. The population in this trial represents a large subset of patients who have a clear unmet clinical need,” said Dr Frederick Vivino from the University of Pennsylvania Perelman School of Medicine in Philadelphia, Pennsylvania, US, in a press release. [https://ir.horizontherapeutics.com/news-releases/news-release-details/horizon-therapeutics-plc-announces-phase-2-trial-evaluating-0]

Hence, Baldini and her team conducted a double-blind, placebo-controlled, parallel-arm, phase II trial involving 109 patients (mean age 49.9 years, 94.5 percent female) with Sjögren’s syndrome who had an unacceptable symptom burden despite limited systemic disease activity (second population of the study). Participants were randomly assigned to receive either dazodalibep 1,500 mg (n=54) or placebo (n=55) during stage I. Baseline mean ESSPRI and ESSDAI** scores were 6.9 and 2.8, respectively. [EULAR 2023, abstract LB0003]

At the end of stage I (day 169), patients treated with dazodalibep achieved a 1.8-point reduction in their ESSPRI scores from baseline compared with a 0.53-point reduction observed in those treated with placebo, and this translated to a statistically significant mean difference of -1.27 (p=0.0002).

This result led to significant improvements across the three individual domains of ESSPRI (dryness: -1.9 vs -0.8; p<0.01; fatigue: -1.7 vs -0.3; p<0.01; and pain: -1.8 vs -0.4; p<0.01) among those on dazodalibep vs those on placebo at day 169.

A significantly higher ESSPRI response rate, defined as ≥1-point or 15-percent reduction in ESSPRI score from baseline, was observed in the dazodalibep arm than the placebo arm at day 169 (66.7 percent vs 32.7 percent; odds ratio, 4.0; p=0.0008).

With regard to quality-of-life measures, those treated with dazodalibep had a significantly greater improvement in FACIT***-Fatigue score from baseline to day 169 compared with placebo (least square [LS] mean difference, 5.3; p=0.095).

Moreover, OSDI⁺ and PGIS⁺⁺ were numerically greater with dazodalibep compared with placebo (LS mean difference 5.43; p=0.1936 and -0.2; p=0.1781, respectively), though these findings did not reach statistical significance, Baldini noted.

In terms of safety, the incidence of adverse events (AEs) was comparable between the dazodalibep and placebo arms (68.5 percent vs 69.1 percent). Only one patient discontinued treatment with dazodalibep.

All AEs were considered mild through day 169, with no deaths reported in either treatment arm. “Dazodalibep therapy was generally safe and appeared to be well tolerated,” noted Baldini.

“Overall, the study met its primary endpoint,” said Baldini. “In patients with an unacceptable symptom burden with limited extraglandular organ involvement, a 24-week course of dazodalibep produced statistically significant improvement in the ESSPRI score compared with the control arm.”

“Dazodalibep is a potential new therapy for patients with Sjögren’s that have an unacceptable symptom burden with limited extraglandular organ involvement,” Baldini noted.

“However, larger clinical trials are warranted to confirm the clinical efficacy and safety of dazodalibep therapy in this subgroup of patients with predominant glandular features, pain, and fatigue that have largely been excluded from recent trials,” she added.

*ESSPRI: EULAR Sjögren’s Syndrome Patient Reported Index

**ESSDAI: EULAR Sjögren’s Syndrome Disease Activity Index

***FACIT: Functional Assessment of Chronic Illness Therapy

⁺OSDI: Ocular Surface Disease Index