Horizon Therapeutics plc announced that the second population in its phase 2 clinical trial assessing dazodalibep for Sjögren’s syndrome (SS) met its primary endpoint.
What is dazodalibep?
Dazodalibep is a CD40 ligand antagonist that blocks T-cell interaction with CD40-expressing B-cells, causing disruption in the overactivation of the CD40 ligand co-stimulatory pathway. In tumor-bearing hosts, CD40 agonists can trigger immune responses to fight against tumor-associated antigens. (via)
Tell me about the trial participants.
The phase 2 trial studied two patient populations diagnosed with SS. The first included 74 participants with moderate-to-high systemic disease activity—defined by a European Alliance of Associations for Rheumatology (EULAR) SS disease activity index (ESSDAI) score of ≥ 5—and the second population included 109 participants with moderate-to-severe subjective symptoms—defined by an EULAR SS patient-reported index (ESSPRI) score of ≥ 5 and residual stimulated salivary flow but with an ESSDAI score of < 5.
How about the trial?
The study consisted of three time periods: screening (4 weeks); treatment (40 weeks); and follow up (12 weeks). During treatment, participants in both populations were randomized 1:1 to be administered an intravenous dose of dazodalibep or a placebo for 24 weeks (Stage 1).
After Stage 1 completion, patients who had initially received a dose of dazodalibep received a placebo, and vice versa, for the remaining 16 weeks of the trial (Stage 2).
All participants were tracked for at least 12 weeks following their last drug dosage. (via)
Wait … what happened to the first population?
Horizon announced in September 2022 that the first population of participants met its primary endpoint, with a 6.3-point and 4.1-point reduction in their ESSDAI scores for patients treated with dazodalibep and placebo, respectively, at Day 169. (via)
How about this second population?
The population of patients with moderate-to-severe SS achieved its primary endpoint. At Day 169, patients treated with dazodalibep achieved a 1.8-point reduction in their ESSPRI scores versus a 0.53-point reduction for placebo-treated patients.
Any adverse events?
The most common adverse events (though Day 169) were COVID-19 infection, nasopharyngitis, and anemia.
Significance?
These latest results make this the only phase 2 trial to meet primary endpoint in both patient populations. With no current FDA-approved treatments for SS, dazodalibep has the potential to be a game-changer for managing patients suffering from this condition.
What’s next?
Horizon plans on working with the FDA to design a phase 3 program for dazodalibep to launch in 2023, ahead of its previous timeline.