Favorable Benefit to Risk Ratio Noted for Iberdomide in Patients With Systemic Lupus Erythematosus

Treatment with iberdomide has a favorable benefit to risk ratio in patients with systemic lupus erythematosus (SLE), according to study results published in Lupus Science & Medicine.

Researchers evaluated the safety, pharmacokinetics, pharmacodynamics and efficacy of iberdomide in patients with active SLE in a 12-week, double-blind, placebo-controlled, dose-escalation study, followed by a 2 year active treatment-extension phase (ClinicalTrials.gov Identifier: NCT0218040).

A total of 42 patients with active SLE were enrolled in the dose-escalation phase and were randomly assigned to receive placebo or oral iberdomide at 0.3 mg every other day, 0.3 mg once daily, 0.6 mg and 0.3 mg alternating once daily, or 0.6 mg once daily. Of these participants, 33 completed the phase and 17 were enrolled into the active treatment-extension phase.

Primary study endpoints were safety and tolerability of iberdomide.

The most common treatment-emergent adverse events during the dose-escalation phase were nausea, occurring in 20.6% of the treatment group and 12.5% of the control group; diarrhea, which occurred in 17.6% of the treatment and 12.5% of the control groups; and upper respiratory tract infection, which occurred in 11.8% and 12.5% of the treatment and control groups respectively. The severity of these events was typically mild or moderate and they were more common in the higher dose groups of both study phases.

Physician’s Global Assessment (PGA) and Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) activity scores improved compared with baseline and placebo in all treatment groups during the dose-escalation phase. A trend toward score improvements continued in the treatment-extension phase.

Researchers noted a dose-dependent reduction in total B cells and plasmacytoid dendritic cells because of iberdomide treatment in the dose-dependent phase, and improvements in CLASI scores correlated with the depletion of plasmacytoid dendritic cells.

The study was limited by the small sample size, the long duration between the study phases, and the short duration of the dose-dependent phase. The patient population enrolled in the study had mild disease activity, with the exclusion of patients who were receiving prednisone of greater than10 mg/day or any background immunosuppressants. At baseline, patients in the placebo group had lower CLASI and PGA scores, which limited the ability to discern treatment differences for these outcomes.

According to the researchers, “This phase 2a study provides proof-of-concept findings suggesting a [favorable] benefit/risk ratio of iberdomide in patients with SLE.” They added, “…findings from this proof-of-concept study support further investigation of iberdomide in patients with SLE.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Reference

Furie RA, Hough DR, Gaudy A, et al. Iberdomide in patients with systemic lupus erythematosus: a randomised, double-blind, placebo-controlled, ascending-dose, phase 2a study. Lupus Sci Med. 2022;9(1):e000581. doi:10.1136/lupus-2021-000581