Novel non-antibody fusion protein effective Sjögren’s syndrome

In the phase 2 ALISS trial, dazodalibep led to a significant reduction of the symptom burden in participants with Sjögren’s syndrome. These results support further development of the drug in a phase 3 trial.

As Prof. Eugene William St. Clair (Duke University Medical Center, NC, USA) pointed out, a substantial part of patients with Sjögren’s suffer from an unacceptable symptomatic burden (equaling a score in the EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) ≥5) and limited extraglandular organ involvement. The ESSPRI focuses on the symptoms of dryness, fatigue, and pain. Moreover, these participants have largely been excluded from recent therapeutic trials, which only enrolled subjects 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 costimulatory signals between immune cells, including T-cells, B-cells, and antigen-presenting cells. The drug was assessed in the randomised, double-blind, placebo-controlled, parallel-arm study ALISS (NCT04129164) in 2 different populations of adults with Sjogren’s syndrome. Dr Chiara Baldini (University of Pisa, Italy) 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 randomised 1:1 to placebo or dazodalibep, and 102 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 3 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,” Dr Chiara Baldini (l’Università degli Studi Di Pisa, Italy) said.

The drug was also relatively well tolerated, with the most frequently reported adverse events occurring in ≥5% of treated subjects being COVID-19, nasopharyngitis, anaemia, 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.

1. Clair EW, et al. Dazodalibep in Sjogren’s subjects with an unacceptable symptom burden: safety and efficacy from a phase 2, randomized, double-blind study. LB0003, EULAR 2023, 31 May – 3 June, Milan, Italy.

Copyright ©2023 Medicom Medical Publishers



Posted on 5 June, 202317 August, 2023