Background/Purpose:

Epratuzumab, a monoclonal antibody targeting CD22, is in development for the treatment of systemic lupus erythematosus (SLE). Two randomized, double-blind trials (ALLEVIATE 1 and 2) were prematurely terminated due to interruption of drug supply. SL0006 was an open-label extension study in which patients previously enrolled in the ALLEVIATE trials received epratuzumab. This abstract reports final long-term safety and efficacy data from SL0006 in patients with moderately-to-severely active SLE.

Methods:

Patients (n=29) in SL0006 received 12-week cycles of epratuzumab 360 mg/m² (2 infusions, at days 1 and 8 of each cycle). Ten were from ALLEVIATE-1 and had severe (BILAG A) SLE activity in ≥ 1 body/organ system, while 19 were from ALLEVIATE-2 with moderate (BILAG B) activity in ≥ 2 body/organ systems. All patients were eligible for enrollment in SL0006, subject to investigator’s judgment of treatment benefit. There was a median delay in epratuzumab dosing of 165 days (range 1–400) between premature termination of the ALLEVIATE studies and entry into SL0006. Assessments were every 4 weeks from screening (Visit 1; V1).

Results:

Patients were aged 22–61 years; almost 90% were women, and 72% were of European descent (79% Caucasian). Median study duration was 4.0 years (0.3–5.3). Median corticosteroid dose (range) at the start of ALLEVIATE (baseline) was 21 mg/day (10–80), and by the start of SL0006 (V1) dose reduced to 7.5 mg/day (0–30). Lower levels of corticosteroid were maintained to the last visit (0–105). Median (range) total BILAG scores decreased throughout the study from baseline of 17 (12–30) (last visit 12 [1–34]). BILAG improvement from baseline was maintained from SL0006 V1 to end of study, with most V1 BILAG A/B grades improving to C/D at least once during the study (Table). Median (range) total SLEDAI scores also decreased throughout the study from baseline of 10 (4–26) (last visit 8 [0–16]). SLEDAI improvement from baseline was also maintained from V1 to end of study. Median patient and physician global assessments of disease activity each improved from 3.0 and 2.8, respectively, at baseline by a median of 1.0 categories. Median reductions in absolute B-cell (CD19+) counts were observed throughout the study, from screening (34.0% reduction) until the last visit (45.0% reduction). All patients reported at least 1 AE, with 14 patients (48.3%) experiencing at least one SAE. Four patients (13.8%) discontinued because of AEs. The most frequent AEs, occurring in at least 5% of subjects, were infections and infestations (upper respiratory tract infections 58.6%, and sinusitis, nasopharyngitis, urinary tract infections [all 37.9%], anxiety, and nausea [both 34.5%]).

Conclusion:

With continued administration, epratuzumab maintained improvements in SLE disease activity over approximately 4 years, with a tolerable safety profile. No new safety concerns were identified.