The findings of a 24-week, phase 2 trial published in the recent issue of the New England Journal of Medicine have demonstrated that iberdomide at a dose of 0.45 mg contributed to a significant reduction in SLE disease activity.
Merrill and co-researchers carried out the study by randomly assigning SLE patients in 2:2:1:2 ratio to receive 0.45, 0.30, or 0.15 mg of iberdomide or placebo for 24 weeks once in daily basis along with other standard-of-care medications. The corresponding percentages of subjects noted with SLE Responder Index (SRI-4) in 0.45 mg, 0.30-mg, 0.15-mg and the placebo groups were 54%, 40%, 48% and 35% respectively. No significant differences were observed upon comparing the groups that received the lower doses of iberdomide with placebo. The drug-related adverse events noted were urinary tract and upper respiratory tract infections, and neutropenia.
Iberdomide, a cereblon modulator, acts by enhancing degradation of the transcription factors Ikaros and Aiolos. Previous studies have also reported the drug’s antitumor and immunostimulatory activities in lenalidomide- and pomalidomide-resistant multiple myeloma cells. The present study findings showed that iberdomide 0.45 mg helped in a major proportion of patients to acheive an SRI-4 response compared to placebo. However, further larger, and longer trials are required to find out about efficacy and safety of iberdomide in SLE.
Reference: Merrill JT, Werth VP, Furie R, van Vollenhoven R, Dörner T, Petronijevic M, Velasco J, Majdan M, Irazoque-Palazuelos F, Weiswasser M, Korish S, Ye Y, Gaudy A, Schafer PH, Liu Z, Agafonova N, Delev N. Phase 2 Trial of Iberdomide in Systemic Lupus Erythematosus. N Engl J Med. 2022 Mar 17;386(11):1034-1045