Kiniksa Pharmaceuticals, Ltd. announced plans to initiate a Phase 2b trial with abiprubart in Sjogren?s Disease. Additionally, the company announced data from Cohort 4 of the Phase 2 clinical trial of abiprubart in rheumatoid arthritis. Abiprubart is an investigational humanized anti-CD40 monoclonal antibody designed to inhibit CD40-CD154 (CD40 ligand) interaction.

Phase 2b Clinical Trial of Abiprubart in Sjogren?s Disease: Kiniksa is planning to initiate a randomized, double-blind, placebo-controlled Phase 2b trial designed to evaluate the treatment response of chronic subcutaneous (SC) administration of abiprubart in patients with Sjogren?s Disease. The placebo-controlled portion of the trial will randomize approximately 201 patients in a 1:1:1 ratio to receive abiprubart 400 mg SC biweekly, 400 mg SC monthly, or placebo over a period of 24 weeks. The primary endpoint will be change from baseline in EULAR Sjogren?s Syndrome Disease Activity Index (ESSDAI) versus placebo at Week 24.

Subsequently, patients will enter a long-term extension in which all patients will receive active treatment for an additional 24 weeks. The trial is expected to initiate in the second half of 2024. Abiprubart Phase 2 Rheumatoid Arthritis Data: The Phase 2 rheumatoid arthritis trial uses a randomized, double-blind, placebo-controlled design to evaluate pharmacokinetics (PK), safety, and efficacy of chronic SC administration of abiprubart and to provide optionality to evaluate abiprubart across a range of autoimmune diseases.

The trial enrolled patients with active rheumatoid arthritis who had an inadequate response or were intolerant to a Janus kinase inhibitor (JAKi) or at least one biologic disease-modifying anti-rheumatic drug (bDMARD). Following previously reported topline data, Kiniksa announced final data from the first three cohorts of the clinical trial: In Cohorts 1 and 2, multiple doses of abiprubart were well-tolerated and enabled the proof-of-concept portion of the study. In the Cohort 3 abiprubart 5 mg/kg SC weekly dose group (n=27), the Least Squares (LS) mean change [95% confidence interval (CI)] from baseline in Disease Activity Score of 28 Joints Using C-reactive Protein (DAS28-CRP) at Week 12 was -2.17 [-2.60, -1.74] points, compared to -1.61 [-2.04, -1.17] points in placebo recipients (n=26), (LS Mean Difference = -0.57, p=0.0470).

In the Cohort 3 abiprubart 5 mg/kg SC biweekly dose group (n=25), the LS mean change [95% CI] from baseline in DAS28-CRP at Week 12 was -1.96 [-2.40, -1.52] points, compared to -1.61 [-2.04, -1.17] points in placebo recipients (n=26), (LS Mean Difference = -0.36, p=0.2124). There was a statistically significant reduction of over 40% in Rheumatoid Factor, a clinical marker of disease activity and an autoantibody pharmacodynamic marker of CD40 target engagement, in both Cohort 3 abiprubart dose groups (p<0.0001). Abiprubart was well-tolerated, with no dose-related adverse experiences observed.

Kiniksa announced topline data from the fourth cohort of the clinical trial: In the Cohort 4 abiprubart 400 mg SC monthly dose group (n=31), the LS mean change [95% CI] from baseline in DAS28-CRP at Week 12 was -1.87 [-2.54, -1.21] points, compared to -1.30 [-1.98, -0.62] points in placebo recipients (n=20), (LS Mean Difference = -0.58, p=0.109). There was a statistically significant reduction of approximately 40% in Rheumatoid Factor in the abiprubart group (p=0.0003). As in the first three cohorts, abiprubart was well-tolerated, and no dose-related adverse experiences were observed.

Additionally, Kiniksa announced a post-hoc analysis of data pooled from the Cohort 3 and Cohort 4 abiprubart and placebo groups: In the pooled abiprubart group (n=83), the LS mean change [95% CI] from baseline in DAS28-CRP at Week 12 was -2.04 [-2.34, -1.74] points, compared to -1.52 [-1.88, -1.16] points in placebo recipients (n=46), (LS Mean Difference = -0.52, nominal p=0.010).