USA: Findings from a Recent Trial on Ianalumab

Findings from a recent trial showed ianalumab to be safe and well-tolerated in patients with moderate to severe primary Sjögren's syndrome. The study was published in the journal The Lancet on November 30, 2021.

Sjögren's syndrome is an immune system disorder characterized by dry eyes and mouth, systemic features, and reduced quality of life. Currently, there are no disease-modifying treatments. A new biologic, ianalumab (VAY736), with two modes of suppressing B cells, has previously shown preliminary efficacy.

In the study, Prof Simon J Bowman, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK, and colleagues aimed to assess the safety and efficacy of different subcutaneous doses of ianalumab in patients with moderate to severe primary Sjögren's syndrome. They found that the study met its primary objective, showing a dose-related decrease in disease activity as measured by ESSDAI at week 24.

"To our knowledge, this is the first large, randomized, controlled trial in primary Sjögren's syndrome that met its primary endpoint, and its results mean there is potential for more studies of this mechanism in the future," wrote the authors.

The researchers designed a randomized, parallel, double-blind, placebo-controlled, phase 2b dose-finding study performed in 56 centers in 19 countries. It included patients aged 18–75 years with primary Sjögren's syndrome with moderate to severe disease activity (European Alliance of Associations for Rheumatology [EULAR] Sjögren's Syndrome Disease Activity Index [ESSDAI] score ≥6) and symptom severity (EULAR Sjögren's Syndrome Patient Reported Index score ≥5). They were randomly assigned in the ratio of 1:1:1:1 to receive subcutaneous placebo or ianalumab (5 mg, 50 mg, or 300 mg) every 4 weeks for 24 weeks using a secure, online randomization system.

The primary outcome was the change in ESSDAI score from baseline to 24 weeks in all randomly assigned patients.

293 patients were screened between June 27, 2017, and Dec 06, 2018, 190 of whom were randomly assigned (placebo n=49, ianalumab 5 mg n=47, ianalumab 50 mg n=47, ianalumab 300 mg n=47).

Key Findings

• Statistically significant dose-responses were seen for overall disease activity (ESSDAI score) in four of the five dose-response models tested.
• The ESSDAI score decreased from baseline in all ianalumab groups, with the maximal ESSDAI score change from baseline observed in the ianalumab 300 mg group: placebo-adjusted least-squares mean change from baseline −1.92 points.
• There were four serious adverse events in three patients considered treatment-related (pneumonia [n=1] and gastroenteritis [n=1] in the placebo group; appendicitis plus tubo-ovarian abscess in the same patient in the ianalumab 50 mg group).

"The study met its primary objective, showing a dose-related decrease in disease activity as measured by ESSDAI at week 24," concluded the authors. "Overall, ianalumab was well-tolerated and safe, with no increase in infections."

Reference

The study titled, "Safety and efficacy of subcutaneous ianalumab (VAY736) in patients with primary Sjögren's syndrome: a randomised, double-blind, placebo-controlled, phase 2b dose-finding trial," was published in the journal The Lancet.

DOI: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02251-0/fulltext