Anti-CD40 Therapy in Sjögren's Disease

Jack Cush, MD

Aug 13, 2024 12:01 pm

Sjögren's disease is a chronic autoimmune condition without a clear effective therapy - DMARD or biologic. The TWINSS study has demonstrated the safety and efficacy of iscalimab, a monoclonal antibody against CD40, in a phase 2 randomized clinical trial of active Sjögren's disease (SD).

This randomised, double-blind, placebo-controlled study enrolled adults with SD meeting the 2026 ACR/EULAR 2016 criteria. The study enrolled 2 cohorts:

Cohort 1: dose-ranging study of SD patients with a EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) score of 5 or higher and a EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) score of 5 or higher. Patients received either subcutaneous iscalimab 150 mg, 300 mg, 600 mg, or placebo.
Cohort 2: patients with an ESSDAI score of less than 5, ESSPRI (dryness or fatigue) score of 5 or higher, and Impact of Dry Eye on Everyday Life score of 30 or higher were randomly assigned to iscalimab 600 mg or placebo.
The primary objectives were to demonstrate a dose–response relationship of iscalimab based on the change in ESSDAI from baseline to week 24 in cohort 1 and the effect of iscalimab 600 mg on ESSPRI at week 24 in cohort 2.

A total of 173 patients were treated in cohort 1 (44 to iscalimab 150 mg, 43 to 300 mg, 43 to 600 mg, and 43 to placebo) and 100 in cohort 2 (50 to each group).

Cohort 1 results:

a significant dose–response relationship was shown
At week 24, ESSDAI decreased all three doses of iscalimab; 150 mg and 600 mg doses

Cohort 2 results:

ESSPRI trended towards improvement with iscalimab 600 mg (but was non-significant; p=0·12)

Serious adverse events were reported in nine patients in cohort 1 and four patients in cohort 2. There were no deaths.

The anti-CD40 mAb Iscalimab, was well tolerated and showed evidence of clinical benefit in this early phase 2 trial. Larger trials are needed to confirm efficacy and safety.

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