Iscalimab (CFZ533) in patients with Sjögren disease: week 24 efficacy and safety results of a randomized, placebo-controlled, phase 2b dose-ranging study

Abstract

Objective

Sjögren disease (SjD) is an autoimmune disease with no approved systemic treatments. Here, the week 24 results from TWINSS, a phase 2b dose-ranging trial assessing the safety and efficacy of multiple doses of iscalimab, an anti-CD40 mAb, in 2 patient populations with SjD are presented.

Methods

Patients fulfilling American College of Rheumatology/European League Against Rheumatism (EULAR) 2016 classification criteria and stimulated salivary flow (SF) rates of ≥0.1 mL/min, were included. In cohort 1 (C1), patients with EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) ≥5 and EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) ≥5 were randomized (1:1:1:1) to placebo or iscalimab 150, 300, or 600 mg subcutaneously once every 2 weeks. In cohort 2 (C2), patients with ESSDAI <5, ESSPRI (fatigue or dryness) ≥5, and impact of dry eye on everyday life ≥30 were randomized (1:1) to placebo or iscalimab 600 mg. Multiple comparison procedure–modeling was used to assess the dose response of ESSDAI change from baseline (C1) and a mixed model for repeated measures to estimate the placebo-adjusted mean change from baseline of ESSDAI (C1 and C2).

Results

In total, 173 patients were assigned to C1 and 100 to C2. In C1, ESSDAI change from baseline at week 24 showed significant improvements with iscalimab 150 and 600 mg compared with placebo (least square mean difference [Δ]: −3.0 and −2.9, respectively; P < .005); the 300-mg dose showed a similar trend (Δ: −1.4; P = .16). The primary objective of a significant dose-response based on ESSDAI change from baseline at week 24 (P = .004) with a log-linear dose response was met. ESSPRI, FACIT-F, and SF rates showed trends of improvement with iscalimab. In C2, the primary objective of ESSPRI change from baseline showed a strong trend (Δ: −0.57; P = .12) toward improvement; dryness (P = .016) and fatigue (P = .067) were the response drivers. A significant increase in SF rates was observed with iscalimab. At week 24, SAE rates in C1 (placebo, iscalimab 150, 300, and 600 mg) were 2.3%, 2.3%, 7.1%, and 9.1%, respectively; in C2, the rate was 4% for both groups.

Conclusions

Iscalimab was well tolerated and showed improvements over placebo in 2 distinct SjD populations, and important signals for improvement in salivary flow.