UCB announces new results from phase 2b open-label extension study evaluating the long-term effects of epratuzumab in SLE
Brussels (Belgium), June 13th 2013, 0700 CEST – UCB today 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 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 Immunomedics Inc. (NASDAQ: IMMU), 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 SLE1
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 SLE2
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 SLE1
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 >0–7.5mg/day or no longer receiving corticosteroids increased (33.5% and 5.9% at baseline and 45.5% and 12.5% respectively, at week 116).
Assessment of immunological parameters to long-term epratuzumab treatment7
Secondary outcome measures in SL0008 also assessed the long-term effect of epratuzumab treatment on B-cells and other immunological parameters.
Median absolute B-cell count decreased by 50% at week 112, compared to EMBLEM™ baseline. CD22 expression on B-cells remained low relative to EMBLEM™ baseline throughout SL0008. No consistent trends were seen in median T cell counts, which remained similar to EMBLEM™ baseline at week 112 and no consistent trends were observed for IgG or IgA which remained within normal levels. IgM levels decreased slightly (-0.21 g/L by week 112). At week 48, there was little correlation between BILAG improvement rate and B-cell levels. The moderate reduction in B-cell counts and the lack of correlation supports B-cell modulation rather than depletion as a mode of action for epratuzumab.
Results presented above from the long-term extension of EMBLEM™ should be viewed in the context of an open-label study without placebo control. Further studies are warranted to confirm these findings.
Notes to editors
Epratuzumab, licensed from Immunomedics Inc., is an investigational medicine in clinical development for the treatment of SLE. Epratuzumab is the first monoclonal antibody that targets CD22, a B-cell specific protein which regulates B-cell activity through the BCR.3 Epratuzumab is not approved for the treatment of SLE by any regulatory authority worldwide.
SLE or lupus, is a complex, systemic, autoimmune disease that affects many different organ systems, including the skin, joints, lungs, kidneys and blood.5 Disease activity and rate of progression of organ system damage is highly variable.3 SLE affects from 20 to 70 people per 100,000 population, and is rare in childhood.8 It is 10 times more common in women than men.8
1. Wallace D., Ordi-Ros J., Neuwelt M. et al. Epratuzumab: sustained safety profile and effect on corticosteroid use on long-term treatment in patients with moderate-to-severe systemic lupus erythematosus: Results from an open label, long-term extension study (SL0008). Presented at the European League Against Rheumatism (EULAR) 2013 Congress. Abstract # THU0277
2. Gordon C., Clowse M., Houssiau F. et al. Epratuzumab maintains improvements in disease activity for over 2 years in patients with moderate-to-severe systemic lupus erythematosus: results from an open-label long-term extension study (SL0008). Presented at the European League Against Rheumatism (EULAR) 2013 Congress. Abstract # THU 0272
3. Wallace D.J., Kalunian K., Petri M.A. et al. Efficacy and safety of epratuzumab in patients with moderate/severe active systemic lupus erythematosus: results from EMBLEM, a phase IIb, randomised, double-blind, placebo-controlled, multicentre study. Ann Rheum Dis. 2013 Jan 12. [Epub ahead of print]
4. Clinical Trials.gov. http://clinicaltrials.gov/ct2/show/NCT00660881?term=SL0008&rank=1 Accessed 10th June 2013
5. Goldenberg D.M., Wallace D.J. Epratuzumab in SLE. http://www.futuremedicine.com/doi/abs/10.2217/ebo.11.86 Accessed 10th June 2013
6. Clinical Trials.gov. http://clinicaltrials.gov/ct2/show/NCT00624351?term=SL0007&rank=2 Accessed 10th June 2013
7. Strand V., Leszczynski P., Keiserman M. et al. Immunologic response to long-term epratuzumab treatment in SL0008, an open-label long-term extension study in patients with moderate-to-severe systemic lupus erythematosus. Presented at the European League Against Rheumatism (EULAR) 2013 Congress. Abstract # THU 0286
8. Pons-Estel G.J., Alarcón G.S., Scofield L. et al. Understanding the epidemiology and progression of systemic lupus erythematosus. Semin Arthritis Rheum. 2010 Feb;39(4):257-68
For further information
Eimear O Brien, Brand Communications, UCB
T +32.2.559.9271, email@example.com
Antje Witte, Investor Relations, UCB
T +32.2.559.9414, firstname.lastname@example.org
France Nivelle, Global Communications, UCB
T +32.2.559.9178, email@example.com
Laurent Schots, Media Relations, UCB
T +32.2.559.9264, firstname.lastname@example.org
UCB, Brussels, Belgium (www.ucb.com) is a global biopharmaceutical company focused on the discovery and development of innovative medicines and solutions to transform the lives of people living with severe diseases of the immune system or of the central nervous system. With more than 8 500 people in about 40 countries, the company generated revenue of EUR 3.4 billion in 2012. UCB is listed on Euronext Brussels (symbol: UCB).
Forward looking statements
This press release contains forward-looking statements based on current plans, estimates and beliefs of management. All statements, other than statements of historical fact, are statements that could be deemed forward-looking statements, including estimates of revenues, operating margins, capital expenditures, cash, other financial information, expected legal, political, regulatory or clinical results and other such estimates and results. By their nature, such forward-looking statements are not guarantees of future performance and are subject to risks, uncertainties and assumptions which could cause actual results to differ materially from those that may be implied by such forward-looking statements contained in this press release. Important factors that could result in such differences include: changes in general economic, business and competitive conditions, the inability to obtain necessary regulatory approvals or to obtain them on acceptable terms, costs associated with research and development, changes in the prospects for products in the pipeline or under development by UCB, effects of future judicial decisions or governmental investigations, product liability claims, challenges to patent protection for products or product candidates, changes in laws or regulations, exchange rate fluctuations, changes or uncertainties in tax laws or the administration of such laws and hiring and retention of its employees. UCB is providing this information as of the date of this press release and expressly disclaims any duty to update any information contained in this press release, either to confirm the actual results or to report a change in its expectations.
There is no guarantee that new product candidates in the pipeline will progress to product approval or that new indications for existing products will be developed and approved. Products or potential products which are the subject of partnerships, joint ventures or licensing collaborations may be subject to differences between the partners. Also, UCB or others could discover safety, side effects or manufacturing problems with its products after they are marketed.
Moreover, sales may be impacted by international and domestic trends toward managed care and health care cost containment and the reimbursement policies imposed by third-party payers as well as legislation affecting biopharmaceutical pricing and reimbursement.
Stay up-to-date on the latest news and information from UCB