medwireNews: Findings from a phase 2 trial suggest that iscalimab, an anti-CD40 antibody that blocks the CD40–CD154 pathway, warrants further investigation as a treatment option for primary Sjögren’s syndrome.
“To our knowledge, this is the first randomised, placebo-controlled proof-of-concept study of a new investigational drug for primary Sjögren’s syndrome that indicates preliminary efficacy,” say the investigators.
The trial, involving participants from 10 centers across Europe and the USA, included one cohort of 32 patients who were randomly assigned to receive intravenous iscalimab 10 mg/kg (n=21) or placebo (n=11) at weeks 0, 2, 4, and 8, and one cohort of 12 patients who were given either subcutaneous iscalimab 3 mg/kg (n=8) or placebo (n=4) on the same dosing schedule.
As reported in The Lancet Rheumatology, patients treated with intravenous iscalimab 10 mg/kg experienced a significantly greater improvement in EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) score from baseline to week 12 than those given intravenous placebo, with a baseline-adjusted average difference of 5.21 points.
The average ESSDAI score decreased from 10.6 points at baseline to approximately 5.0 points at week 12 in the intravenous iscalimab group, and from 11.0 to approximately 10.0 points in the placebo arm. After week 12, all participants received iscalimab for the remainder of the study; patients treated with the anti-CD40 inhibitor throughout the trial experienced continued reductions in ESSDAI score, while those who switched from placebo experienced reductions after week 12.
Conversely, Peter Gergely (Novartis Institutes for Biomedical Research, Basel, Switzerland) and co-researchers did not observe a significant difference in the improvement in ESSDAI score among patients treated with subcutaneous iscalimab 3 mg/kg versus placebo, but this cohort was not fully powered to assess efficacy.
The team reports that iscalimab was well tolerated in both cohorts, with a similar number of adverse events (AEs) in the active treatment and placebo groups. In all, 33% of patients given intravenous iscalimab and 88% of those given the subcutaneous form experienced AEs, as did 55% and 100% of patients in the corresponding placebo groups. The most common AE in both cohorts was upper respiratory tract infection.
“[W]e found no evidence of cytopenias, injection site reactions, thromboembolic events, or increased risk for infections, which have previously been observed with biologicals targeting CD154,” say Gergely and colleagues.
Taken together, these “preliminary findings suggest a role of CD40–CD154 interactions in primary Sjögren’s syndrome pathology and add to the evidence that this novel anti-CD40 antibody deserves further research into whether it can deliver clinically meaningful benefit in patients with primary Sjögren’s syndrome in longer trials with more patients,” conclude the researchers.
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