Dörner, Thomas, Posch, Maximilian, Li, Yue, Petricoul, Olivier, Cabanski, Maciej, Valentin, Marie-Anne, Simonett, Claudia, Mooney, Louise, Gram, Hermann, Wagner, Frank and Oliver, Stephen (2019) Treatment of primary Sjögren’s syndrome with ianalumab (VAY736) Targeting B cells by BAFF receptor-blockade coupled with enhanced, antibody-dependent cellular cytotoxicity. Annals of the rheumatic diseases., 78 (5). pp. 641-647.

Abstract

Objectives
To evaluate the efficacy and safety of VAY736 (ianalumab), a B-cell-depleting, BAFF-receptor blocking, monoclonal antibody, in patients with active primary Sjögren’s syndrome in a double blind, placebo-controlled, phase II, single center study.
Methods
Patients with primary Sjögren’s syndrome (pSS), disease activity ESSDAI 6, were randomized to VAY736 single infusion at either 3 mg/kg (n=6), 10 mg/kg (n=12), or placebo (n=9). Outcomes were measured blinded at baseline and weeks 6, 12, 24, and unblinded at end of study (EoS) when B-cells numbers had recovered. Clinical outcomes included ESSDAI, ESSPRI, salivary flow rate, ocular staining score, physician global assessment and patient assessments of fatigue and general quality of life. Laboratory-based measures included circulating leucocyte subsets and markers of B cell activity.
Results
A similar trend showing positive therapeutic effect by VAY736 was observed across the primary clinical outcome (ESSDAI) and all secondary clinical outcomes (ESSPRI, MFI, SF3-36, global assessments by physician and patient) versus the placebo-treated group. Rapid and profound B-cell depletion of long lasting duration occurred after a single infusion of VAY736 at either dose. Serum Ig light chains decreased with return to baseline levels at EoS. Changes in some clinical outcomes persisted through to EoS in the higher dose group. Adverse effects were largely limited to mild-to-moderate infusion reactions within 24 hours of VAY736 administration.
Conclusions
Overall results in this single dose study suggest potent and sustained B-cell depletion by VAY736 could provide therapeutic benefits in pSS patients without major side effects.

Item Type:	Article
Date Deposited:	18 Jun 2019 00:45
Last Modified:	18 Jun 2019 00:45
URI:	https://oak.novartis.com/id/eprint/38114