Background/Purpose:

In phase 2b trials, epratuzumab,
a humanized anti-CD22 mAb that modulates B cell signaling without total B cell depletion,
significantly improved disease activity in patients (pts) with
moderate-to-severe SLE.¹ We report the first data from two phase 3,
randomized, double-blind, placebo (PBO)-controlled, multicenter studies of
epratuzumab in active, moderate-to-severe SLE: EMBODY 1™ (SL0009, NCT01262365)
and EMBODY 2™ (SL0010, NCT01261793).
  Methods:

Pts were ≥18
years of age from North and South America, Europe, Australia, Asia and Africa. Entry
requirements included ANA ≥1:80 and/or anti-dsDNA positivity, ≥4 ACR
revised criteria, SLEDAI-2K score ≥6, BILAG-2004 ≥1 A or ≥2 Bs
in mucocutaneous, musculoskeletal or cardiorespiratory domains and receipt of stable
dose CS (5–60 mg/day prednisone equivalent) for ≥5±1 days prior to baseline
(BL). Temporary CS dose increases ≤25% of BL dose were permitted until
Week (Wk) 8. Pts with BILAG A grade renal or central nervous system domain
scores were excluded.

Pts were randomized
1:1:1 to PBO, IV epratuzumab 600 mg every wk (QW) or 1200 mg every other wk
(QOW) in addition to their standard of care (SOC) therapies, stratified by
region and BL disease severity. Drug or PBO was administered for a 4-wk period
at the beginning of each 12-wk treatment cycle for 4 cycles (48 wks total).

The primary endpoint
was the Wk48 responder rate according to the BILAG-based Combined Lupus
Assessment (BICLA) definition, requiring all of the following: BILAG
improvement and no worsening (all BILAG As at entry improved to B/C/D; all Bs
improved to C/D; no new BILAG As and ≤1 new BILAG B), no worsening in
SLEDAI score, no worsening in physician’s global assessment of disease activity,
no disallowed changes in concomitant medications. Secondary efficacy variables included
BICLA response at Wks 36/24/12. CS use was evaluated.

Efficacy data are
presented for the full analysis set. Missing values were imputed using modified
non-responder imputation with missing data incorporated as the worst possible
outcome. Safety data were comprehensively assessed.

Results:

In EMBODY™ 1, 793 pts
were randomized, 786 (99.1%) received study medication, and 528 (66.6%)
completed the study. In EMBODY™ 2, 791 pts were randomized, 788 (99.6%)
received study medication, and 533 (67.4%) completed the study. BL
characteristics were similar across groups (Table A).

Neither study met the
primary endpoint: Wk48 BICLA response rates in epratuzumab+SOC groups were not
statistically different from PBO+SOC groups (Table B). No significant
differences were seen in other efficacy measures.

No new safety signals
were identified (Table B).

Conclusion:

BICLA response rates
at Wk48 were no different in SLE patients treated with epratuzumab+SOC compared
to PBO+SOC. The safety profile of epratuzumab was similar to previous studies.

1.    Wallace D. Ann Rheum Dis
2014;73:183–90