Phase 2 trial supports further investigation of iberdomide for SLE
medwireNews: Findings from a phase 2 study suggest that people with systemic lupus erythematosus (SLE) treated with iberdomide experience sustained improvements in disease activity.
Speaking at the ACR Convergence 2021 virtual meeting, Joan Merrill, from Oklahoma Medical Research Foundation in Oklahoma City, USA, explained that iberdomide is a high-affinity cereblon ligand that promotes degradation of two transcription factors (Aiolos and Ikaros) linked to the development of SLE.
In all, 288 participants with active autoantibody-positive SLE despite conventional treatment were randomly assigned to receive iberdomide at one of three daily doses (0.15 mg, 0.3 mg, or 0.45 mg) or to receive placebo.
Merrill said that the trial met its primary endpoint, with a significantly higher proportion of patients treated with iberdomide 0.45 mg versus placebo achieving an SRI-4 response at week 24 (54.3 vs 34.9%). Responses were enhanced in participants with high type 1 interferon or Aiolos gene signatures at baseline.
After this timepoint, participants in the placebo group were switched to one of the two higher doses of iberdomide, and a total of 214 patients across the treatment groups completed 52 weeks of follow-up.
The presenter said that SRI-4 response rates improved from week 24 to 52 among patients who switched from placebo to iberdomide 0.3 mg (n=36) or 0.45 mg (n=36), with rates of approximately 60% and 58%, respectively, at the 52-week follow-up. Moreover, she pointed out that “all dosing groups either had a greater proportion of responders [at week 52] or sustained the results they achieved in the first half of the study,” including the enhanced responses seen in subgroups according to baseline gene expression.
Merrill added that improvements in the “more stringent” SRI-6 and SRI-8 endpoints, which require 6- or 8-point reductions in SELENA-SLEDAI, respectively, were also sustained or enhanced during follow-up in all treatment groups. A similar pattern of results was seen with FACIT-Fatigue scores, with particularly “dramatic improvements” seen in patients who received the highest iberdomide dose throughout the study, she said.
The most frequently reported adverse events (AEs) with iberdomide were urinary tract infection, upper respiratory tract infection (URTI), and neutropenia. Merrill pointed out that the highest rates of URTI and neutropenia were seen with the highest iberdomide dose, at 14.5% versus 7.1% with the lowest dose for URTI and 13.7% versus 4.8% for neutropenia, suggesting a dose–response association.
A total of 9.4% of participants experienced treatment-emergent AEs leading to discontinuation, most commonly rash or neutropenia.
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2021 Springer Healthcare Ltd, part of the Springer Nature Group
This information is brought to you by medwireNews and is not sponsored by, nor a part of, the American College of Rheumatology.