Date: Sunday, November 5, 2017
Session Type: ACR Concurrent Abstract Session
Session Time: 2:30PM-4:00PM
CC-220 is a high affinity ligand for cereblon with immunomodulatory properties, currently in development for the treatment of Systemic Lupus Erythematosus as well as other autoimmune conditions and multiple myeloma. CC-220 administration results in significant reductions in ikaros (IKZF1) and aiolos (IKZF3), transcription factors which are genetically linked to SLE risk, and are overexpressed in the peripheral blood of SLE patients compared to healthy controls.
CC-220-SLE-001 is a randomized, double-blinded, placebo-controlled, phase 2a dose escalation study to investigate the safety, PK, PD, and efficacy of CC-220 in patients with SLE. Forty-two (42) adult SLE subjects fulfilling SLE ACR criteria, having a history of SLE for ≥6 months and a baseline Safety of Estrogens in Lupus Erythematosus National Assessment–Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score ≥4. Subjects were randomized to placebo or 1 of 4 escalating doses of CC-220 (0.3 mg QOD, 0.3 mg QD, 0.6/0.3 mg alternating QD, or 0.6 mg QD). Efficacy endpoints were exploratory and included Cutaneous Lupus Area and Severity Index (CLASI) skin scores.
CC-220 significantly reduced total CD20+ B cells, immature B cells, unswitched memory B cells, switched memory B cells, BAFFR+ B cells, and plasmacytoid dendritic cells (pDC) by as much as 96%, 91.2%, 59%, 81.4%, 67.5%, and 86.5% (Day 85 median percent change from baseline), respectively. CD4+ and CD8+ T cell counts were not significantly affected, but trended upward, paralleling an increase in plasma cells in those subjects who received the highest dose (0.6 mg). Mean CLASI activity score at baseline was 9.8 with mean reductions in the CLASI activity score at day 85 ranging from 4.3 to 7.8 in the CC-220 treatment groups compared to an increase of 0.4 in the placebo group. The reductions in CLASI activity score were even more significant among subjects who had moderate-to-severe skin involvement (CLASI score ≥10 at baseline). Strong correlations between CLASI improvement and pDC reductions, rather than B cell depletion, were observed in the overall population and in subjects with a baseline CLASI score ≥10.
CC-220 reduces B-Cell subset populations and pDCs in SLE subjects. Treatment with CC-220 resulted in improvement on CLASI score in all treatment groups compared to placebo with strong correlation with pDC depletion. These results support further development of CC-220 in SLE patient population with skin involvement.
- Klein R, et al. Arch Dermatol. 2011;147:203-208.
To cite this abstract in AMA style:Werth VP, Furie R, Gaudy A, Ye Y, Korish S, Delev N, Hough D, Weiswasser M, Choi S, Schafer P. CC-220 Decreases B-Cell Subsets and Plasmacytoid Dendritic Cells in Systemic Lupus Erythematosus (SLE) Patients and Is Associated with Skin Improvement: Pharmacodynamic Results from a Phase IIa Proof of Concept Study [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/cc-220-decreases-b-cell-subsets-and-plasmacytoid-dendritic-cells-in-systemic-lupus-erythematosus-sle-patients-and-is-associated-with-skin-improvement-pharmacodynamic-results-from-a-phase-iia-proof/. Accessed September 20, 2020.
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