A recent phase 2, randomized, double-blind trial study presented at the 2023 EULAR European Congress of Rheumatology and published in Annals of the Rheumatic Diseases has reported that dazodalibep (DAZ), an intravenously administered inhibitor of CD40 ligand, was safe and effective in treating disease activity and symptoms in 2 divergent populations of Sjögren’s syndrome (SS) patients.
The first group included 74 subjects with moderate-to-severe organ involvement or systemic disease activity, as measured by a EULAR SS disease activity Index (ESSDAI) score of five or above. The study looked at changes from baseline in the ESSDAI score as well as the safety of DAZ therapy vs. placebo. The researchers found a significant difference of -2.2 in the ESSDAI score between DAZ-treated patients and placebo (-6.3 ± 0.6 vs -4.1 ± 0.6; P= 0.0167) at day 169 from baseline. The results of post-hoc ESSDAI responder analyses favored DAZ over placebo, with larger numerical differences at the highest levels of response. Moreover, at day 169, the DAZ group outperformed the placebo group regarding EULAR SS patient-reported index score and functional assessment of chronic illness therapy (FACIT) fatigue score. Through day 169, the reported adverse events (AEs) were mostly minor, and safety profiles were similar between DAZ and placebo. The most frequently reported adverse events were COVID-19, diarrhea, dizziness, ligament strain, and upper respiratory infections.
The second group included 109 subjects who had a high symptom burden but only little systemic organ involvement, as indicated by an EULAR SS Patient Reported Index (ESSPRI) score of five or above and an ESSDAI score of less than five. DAZ caused a -1.27 point decline in the ESSPRI score compared to placebo (−1.80 ± 0.23 vs. −0.53 ± 0.23; P= 0.0002) at day 169 from baseline, indicating fewer severe symptoms. The three domains of ESSPRI (Dryness, fatigue, and pain) were significantly superior in the DAZ-treated group compared to the placebo group. In comparison to the placebo group, a considerably higher number of patients in the DAZ group experienced a clinically significant decline in ESSPRI scores, of at least one point or 15% (66.7% vs. 32.7%). The improvement in the FACIT fatigue score from baseline to day 169 was significantly better in the DAZ group compared to the placebo group (8.1 ± 1.4 vs. 2.8 ± 1.4; P= 0.0095). The majority of AEs reported were mild to moderate in severity, and safety profiles were similar between DAZ and placebo, with the most often reported adverse events being COVID-19, nasopharyngitis, and anemia.
In conclusion, the results of this trial provide promising evidence that DAZ is both effective and safe for addressing systemic disease activity and symptoms in patients with SS. These findings highlight the potential of DAZ therapy to meet unmet therapeutic needs in managing this challenging illness, which currently lacks authorized disease-modifying treatments. However, to corroborate these findings and gain a more comprehensive understanding of DAZ’s safety profile and therapeutic effectiveness, larger controlled studies focusing on DAZ treatment for SS are essential. Continued research in this direction holds the key to potentially improving the quality of life for individuals living with SS.
References
- St EW, Clair, Wang L, Alevizos I, Rees W, Baer A, et al. Op0143 Efficacy and Safety of Dazodalibep (vib4920/Hzn4920) in Subjects with Sjögren’s Syndrome: A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Proof of Concept Study. Annals of the Rheumatic Diseases. 2023 Jun 1;82(Suppl 1):95–95.
- Clair EWS, Alevizos I, Rees W, Wang L, Baer A, Ng WF, et al. LB0003 Dazodalibep (VIB4920/HZN4920) in Sjögren’s Subjects with an Unacceptable Symptom Burden: Safety and Efficacy from a Phase 2, Randomized, Double-Blind Study. Annals of the Rheumatic Diseases. 2023 Jun 1;82(Suppl 1):201–201.