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Phase 2 Trial of Iberdomide in Systemic Lupus Erythematosus

List of authors.
  • Joan T. Merrill, M.D.,
  • Victoria P. Werth, M.D.,
  • Richard Furie, M.D.,
  • Ronald van Vollenhoven, M.D., Ph.D.,
  • Thomas Dörner, M.D.,
  • Milan Petronijevic, M.D., Ph.D.,
  • Jorge Velasco, M.D.,
  • Maria Majdan, M.D., Ph.D.,
  • Fedra Irazoque-Palazuelos, M.D.,
  • Michael Weiswasser, M.P.H.,
  • Shimon Korish, M.D.,
  • Ying Ye, Ph.D.,
  • Allison Gaudy, Ph.D.,
  • Peter H. Schafer, Ph.D.,
  • Zhaohui Liu, Ph.D.,
  • Nataliya Agafonova, M.D.,
  • and Nikolay Delev, M.D.

Abstract

Background

Iberdomide, a cereblon modulator promoting degradation of the transcription factors Ikaros and Aiolos, which affect leukocyte development and autoimmunity, is being evaluated for the treatment of systemic lupus erythematosus (SLE).

Methods

Download a PDF of the Research Summary.

In this phase 2 trial, we randomly assigned patients in a 2:2:1:2 ratio to receive oral iberdomide (at a dose of 0.45, 0.30, or 0.15 mg) or placebo once daily for 24 weeks, in addition to standard medications. The primary end point at week 24 was a response on the SLE Responder Index (SRI-4), which was defined as a reduction of at least 4 points in the Systemic Lupus Erythematosus Disease Activity Index 2000 score (a 24-item weighted score of lupus activity that ranges from 0 to 105, with higher scores indicating greater disease activity), no new disease activity as measured on the British Isles Lupus Assessment Group 2004 index, and no increase of 0.3 points or more in the Physician’s Global Assessment score (on a visual-analogue scale ranging from 0 [no disease activity] to 3 [maximal disease]).

Results

A total of 288 patients received the assigned intervention: 81 received iberdomide at a dose of 0.45 mg, 82 received iberdomide at a dose of 0.30 mg, 42 received iberdomide at a dose of 0.15 mg, and 83 received placebo. At week 24, the percentages of patients with an SRI-4 response were 54% in the iberdomide 0.45-mg group, 40% in the iberdomide 0.30-mg group, 48% in the iberdomide 0.15-mg group, and 35% in the placebo group (adjusted difference between the iberdomide 0.45-mg group and the placebo group, 19.4 percentage points; 95% confidence interval, 4.1 to 33.4; P=0.01), with no significant differences between the groups that received the lower doses of iberdomide and the group that received placebo. Iberdomide-associated adverse events included urinary tract and upper respiratory tract infections and neutropenia.

Conclusions

In this 24-week, phase 2 trial involving patients with SLE, iberdomide at a dose of 0.45 mg resulted in a higher percentage of patients with an SRI-4 response than did placebo. Data from larger, longer trials are needed to determine the efficacy and safety of iberdomide in SLE. (Funded by Bristol Myers Squibb; ClinicalTrials.gov number, NCT03161483; EudraCT number, 2016-004574-17.)

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Iberdomide for Systemic Lupus Erythematosus
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Funding and Disclosures

Supported by Bristol Myers Squibb.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.

We thank the patients enrolled in the trial, the clinical trial teams, and Amy Zannikos, Pharm.D., of Peloton Advantage (an OPEN Health company), for writing and editorial assistance with an earlier version of the manuscript.

Author Affiliations

From the Oklahoma Medical Research Foundation, Oklahoma City (J.T.M.); the University of Pennsylvania and the Corporal Michael J. Crescenz VA Medical Center — both in Philadelphia (V.P.W.); Northwell Health, Great Neck, NY (R.F.); Amsterdam University Medical Centers, Amsterdam (R.V.); Charité–Universitätsmedizin, Berlin (T.D.); the Military Medical Academy, Belgrade, Serbia (M.P.); Instituto Centro de Enfermedades Reumáticas, Buenos Aires (J.V.); Independent Public Clinical Hospital Number 4, Medical University of Lublin, Lublin, Poland (M.M.); Centro de Investigación y Tratamiento Reumatológico, Mexico City, Mexico (F.I.-P.); and Bristol Myers Squibb, Princeton, NJ (M.W., S.K., Y.Y., A.G., P.H.S., Z.L., N.A., N.D.).

Dr. Merrill can be contacted at or at the Arthritis and Clinical Immunology Research Program, Mailstop 22, Oklahoma Medical Research Foundation, 825 N.E. 13th St., Oklahoma City, OK 73104.