In the phase 2 ALISS trial, dazodalibep significantly reduced symptom burden in patients with Sjögren’s syndrome.

Eugene William St. Clair, MD

As Eugene William St. Clair, MD, explains, a substantial number of patients with Sjögren’s syndrome experience unacceptable symptomatic burden, measured by a score of 5 or more on the Sjögren’s Syndrome Patient Reported Index (ESSPRI), and limited extraglandular organ involvement. The ESSPRI focuses on the symptoms of dryness, fatigue, and pain. However, these patients have often been excluded from recent clinical trials, which typically enroll patients with moderate to high systemic disease activity.

Dazodalibep is a novel non-antibody fusion protein that acts as an antagonist of CD40L. Thus, it inhibits the co-stimulatory signals between immune cells, including T cells, B cells, and antigen-presenting cells. The drug was assessed in the randomized, double-blind, placebo-controlled, parallel-arm study ALISS (NCT04129164) in two different populations of adults with Sjogren’s syndrome. At EULAR 2023, held May 31 to June 3, in Italy, Chiara Baldini presented the study results of population 2 (n=109), defined as those participants with an unacceptable symptom burden and limited systemic disease activity.

Participants were randomly assigned 1:1 to receive either placebo or dazodalibep, and 102 participants completed the study. At day 169, a statistically significant higher change in ESSPRI total score (primary study endpoint) in participants treated with dazodalibep was seen, compared with placebo (-1.80 with dazodalibep vs -0.53 with placebo; P=0.0002). Similar results were observed for the three individual domains of ESSPRI (dryness, fatigue, and pain). “The study was not powered for secondary outcomes, but despite this, we saw a significant reduction in the fatigue score and a numerical decrease in other secondary outpoints,” Baldini said.

The drug was also relatively well tolerated, with the most frequently reported adverse events occurring in 5% or more of treated subjects being COVID-19, nasopharyngitis, anemia, and diarrhea. Larger clinical trials are now warranted to confirm the clinical efficacy and safety of dazodalibep in this subgroup of patients with Sjögren’s syndrome.

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