Immunomedics, Inc. (Nasdaq: IMMU),a biopharmaceutical company primarily focused on the development of monoclonal antibody-based products for the targeted treatment of cancer, autoimmune and other serious diseases, today reported that UCB (Brussels:UCB), announced new data from an open-label extension (SL0008) of the EMBLEM™ phase 2b study evaluating the long-term effects of epratuzumab treatment in adult patients with moderate-to-severe systemic lupus erythematosus (SLE). The primary outcome of outcome of the open-label extension was to assess the safety of epratuzumab in patients with SLE.^4
Relative to the 12 week, double-blind, placebo-controlled EMBLEM™ study, data from the open-label, long-term extension identified no new safety or tolerability signals.^1 In addition, relative to EMBLEM™ baseline values, secondary outcome data indicated that the efficacy of epratuzumab as measured by reduction in disease activity was maintained over two years.^2 Secondary outcome data also indicated that relative to EMBLEM™ baseline values, treatment over two years with epratuzumab was associated with decreases in corticosteroid use in patients receiving 7.5 mg/day.^1 These data were presented this week at the European League Against Rheumatism 2013 Congress in Madrid, Spain.
Epratuzumab, licensed from the Company to UCB, is an investigational medicine and the first CD-22/B-Cell receptor (BCR) targeted monoclonal antibody to be evaluated in clinical studies for the treatment of SLE. Also known as lupus, SLE is a complex, systemic autoimmune disease that affects many different organ systems, including the skin, joints, lungs, kidneys and blood.^3,5
“In EMBLEM™, a dose-ranging, phase 2b study, reduction in disease activity was observed in patients treated with epratuzumab,” said Professor Daniel J Wallace MD, Clinical Professor of Medicine, Cedars-Sinai Medical Center, California, US. “This double-blind study had a relatively short 12-week, placebo-controlled, treatment period and it was important to accumulate long-term data on epratuzumab in the treatment of SLE. The phase 2b extension study adds new two year open-label data on epratuzumab to that already available from the 12-week, randomized, controlled study.”
EMBLEM™ was designed to identify a suitable dosing regimen for epratuzumab.^6 A total of 227 patients with moderate-to-severe SLE received either: placebo, epratuzumab cumulative dose of 200 mg (100 mg every other week), 800 mg (400 mg every other week), 2400 mg (600 mg weekly), 2400 mg (1200 mg every other week) or 3600 mg (1800 mg every other week).^3,6 In the open-label extension 203 patients from any arm of the EMBELM™ study received 1200 mg epratuzumab at weeks 0 and 2 of 12-week cycles.^1,2,7
Data on epratuzumab presented at EULAR 2013
Evaluation of the safety profile of long-term epratuzumab treatment in patients with moderate-to-severe SLE^1
Safety variables were primary outcome measures in SL0008 and included duration of exposure, adverse events, infusion reactions and infections.
Exposure to epratuzumab was a median 845 days over a median 10 treatment cycles. Adverse events (AEs) caused discontinuation in 29 (14.3%) patients. The most common serious AEs were SLE flare (3.4%), lupus nephritis (2%) and symptomatic cholelithiasis (1.5%). The most common infections/infestations were urinary tract infection (24.6%) and upper respiratory tract infection (23.2%). There were no opportunistic infections and no patterns of specific serious or severe infections.
Evaluation of long-term efficacy of epratuzumab as measured by reduction in disease activity in patients with moderate-to-severe SLE^2
Secondary outcome measures in SL0008 included efficacy as measured by reduction in disease activity, and assessed by: British Isles Lupus Assessment Group (BILAG) improvement, SLE disease activity index (SLEDAI) score, Physician Global Assessment (PGA) score and combined treatment response defined as BILAG improvement without worsening, no SLEDAI worsening and no PGA worsening, relative to EMBLEM™ baseline.
The median BILAG total score was 25.0 at EMBLEM™ baseline and 9.0 at week 108. The score was 14.0 at SL0008 screening. Median SLEDAI score was 12.0 at EMBLEM™ baseline and 4.0 at week 108. The score was 10.0 at SL0008 screening. The median PGA score was 50.0 at EMBLEM™ baseline and 17.5 at week 108 with a score of 31.0 at SL0008 screening. The proportion of patients achieving the combined treatment response was 32.5% at SL0008 screening (n=203) and 60.3% at week 108 (n=116).
Effect of corticosteroid use of long-term epratuzumab treatment in patients with moderate-to-severe SLE^1
Corticosteroid doses were monitored throughout SL0008 and was a secondary outcome measure. Median corticosteroid dose at EMBLEM™ baseline and SL0008 screening was 10.0 mg/day. At week 116, this was 5 mg/day (n=112). Data indicated that treatment over two years with epratuzumab was associated with decreases in corticosteroid use in patients receiving 7.5 mg/day with a corresponding increase in the proportion of patients receiving lower doses or no longer receiving corticosteroids.
The proportion of patients requiring 7.5-20 mg/day and 20 mg/day decreased (49.8% and 10.8% at baseline and 33.9% and 8.0% respectively, at week 116) and the proportion of patients receiving 0–7.5 mg/day or no longer receiving corticosteroids increased (33.5% and 5.9% at baseline and 45.5% and 12.5% respectively, at week 116).
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