Iscalimab Promising for Sjogren's Syndrome

By Marilynn Larkin

February 19, 2020

NEW YORK (Reuters Health) - The anti-CD40 monoclonal antibody iscalimab showed preliminary efficacy against Sjogren's syndrome in a proof-of-concept study.

Although Sjogren's syndrome is a relatively common condition, it is often underdiagnosed, Dr. Peter Gergely of the Novartis Institutes for Biomedical Research in Basel told Reuters Health by email. "Furthermore, the number of clinical trials, especially when compared to rheumatoid arthritis or lupus, is still limited. Currently, there is no systemic therapy available that has been proven efficacious."

"We tested iscalimab, a monoclonal antibody that inhibits CD40, an important regulatory molecule of the immune system," he said. "In (keeping) with several lines of published evidence indicating the role of the CD40 pathway in primary Sjogren's syndrome pathology, our trial suggested the therapeutic potential for CD40 blockade."

Dr. Gergely and colleagues enrolled adults who fulfilled the 2002 American European consensus group diagnostic classification criteria for primary Sjogren's syndrome at 10 centers across Europe.

Safety and tolerability were assessed by adverse events, efficacy and clinical disease activity as measured by the change in European League Against Rheumatism Sjogren's syndrome disease activity index (ESSDAI) score after 12 weeks of treatment.

At weeks 0, 2, 4, and 8, eight patients received 3mg/kg subcutaneous iscalimab and four received placebo (group one); 21 received 10 mg/kg intravenous (IV) iscalimab and 11 received placebo (group two). Participants' mean age was about 52; the first group had no men whereas the second group had two. Mean baseline ESSDAI was somewhat lower in group two, and use of concomitant medications was higher.

Adverse events were similar between iscalimab and placebo groups, according to the Lancet Rheumatology report. Adverse events occurred in all patients in group one, and in group two, in 52% of those taking IV iscalimab and 64% of those taking placebo.

Two serious adverse events unrelated to iscalimab were reported: bacterial conjunctivitis in group one and atrial fibrillation in group two.

IV iscalimab led to a mean reduction of 5.21 points in the ESSDAI score compared with placebo, whereas no significant differences in the score were seen between subcutaneous iscalimab and placebo.

Dr. Gergely said, "Although this was a small exploratory trial.... the positive proof of concept (encouraged) us to continue the development of iscalimab for this indication. Further evidence of safety and efficacy, and data regarding dosing of iscalimab, will be provided in a larger phase 2b trial, which is currently ongoing."

Dr. Alan Baer of Johns Hopkins Medicine, in Baltimore, author of a related editorial, told Reuters Health by email, "The trial showed promising results that need to be confirmed. There was an imbalance in the baseline features of the patients in the two treatment groups...that might have resulted in a 'false' positive result - but we need to do more studies to assess."

The study was funded by Novartis. Dr. Gergely and 11 coauthors were employees at the time of the study and four coauthors have received fees from the company. Dr. Baer was also a consultant to the company.

SOURCE: The Lancet Rheumatology, online January 23, 2020.