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Epratuzumab phase IIb data demonstrated sensitivity of BICLA, a novel BILAG-based composite endpoint

  • The British Isles Lupus Assessment Group (BILAG) index is a comprehensive, validated tool for assessing lupus disease activity1,2 and is listed in FDA guidance as the preferred index when studying disease activity in clinical trials3
  • The BILAG-based Combined Lupus Assessment (BICLA) was supported in the EMBLEM™ study4
  • BICLA is being used as the 48-week primary efficacy variable in the EMBODY™ phase III studies4

BRUSSELS/CHICAGO, November 8th, 2011 - UCB (EURONEXT: UCB) and U.S. based partner Immunomedics Inc. (NASDAQ:IMMU) today announced data, at the 75th Annual Scientific Meeting of the American College of Rheumatology (ACR) in Chicago, that supported the BILAG-based Combined Lupus Assessment (BICLA) as a clinically meaningful composite measure of systemic lupus erythematosus (SLE) disease activity.4

“Evaluating disease activity in lupus clinical trials is challenging, because lupus has a complex pathophysiology, is highly variable between individuals, and has an unpredictable disease course,” commented Daniel J. Wallace, M.D., Clinical Professor of Medicine, Cedars-Sinai/David Geffen School of Medicine at UCLA. He added, “Following confirmation of the BICLA in the EMBLEM™ study we now have a sensitive, clinically meaningful composite measure of disease activity.”

The EMBLEM™ study was designed to evaluate the efficacy and safety of the investigational product epratuzumab (in combination with immunosuppressants) in SLE, identify an optimal dose and regimen for further studies, and assess the performance of the new BILAG-based Combined Lupus Assessment (BICLA) composite endpoint.4,5

The BICLA was developed based on input from an expert panel that evaluated the characteristics of disease activity indices (DAIs) commonly used in SLE trials and previous experience with DAIs to evaluate the efficacy of epratuzumab in clinical trials. It requires patients to meet response criteria across three assessment tools: (1) the BILAG-2004 index (2) the SLEDAI index and (3) a physician’s global assessment (PGA). BICLA responders must achieve BILAG disease activity improvement across all eight body systems with no worsening in BILAG or other disease activity indexes at the same time point, and no treatment failure at any time point.4

In the EMBLEM™ study, all epratuzumab doses, which ranged from 200mg to 3600mg dose administered during one 12-week treatment cycle had numerically superior BICLA response rates compared to placebo at week 12. For patients receiving epratuzumab at a cumulative dose of 2400mg there was meaningful and statistically significant* reductions in disease activity.4,5

The results from the EMBLEM™ study demonstrated that the BICLA, whose components require clinical assessment, physician assessment, laboratory assessment, and recording of medication use, is a sensitive, clinically meaningful composite measure of SLE disease activity and may help to guide the design of future trials in SLE.

In the EMBLEM™ study, the percentage of patients experiencing at least 1 serious adverse event was similar between the epratuzumab-treated group (7.0%) and placebo treated group (7.9%).5

Epratuzumab is a humanised monoclonal antibody targeting CD22 and modulating B-cell activity and as an investigational product is being studied in the treatment of patients with moderate to severe SLE.Although the exact role of CD22 is not fully understood, it is considered to be a regulator of B-cell function. B-cells are known to contribute to SLE by producing antibodies against the body's own cells and tissues, causing the immune system to turn on itself, resulting in inflammation and tissue damage. Epratuzumab is an anti-B-cell therapeutic, because of its ability to modulate B-cell function without depleting a large portion of these lymphocytes.

* This study was not powered to detect statistical differences between treatment arms (p values were not adjusted for multiple comparisons and are based on an exploratory post-hoc analysis).

For further information

Scott Fleming, Global Communications Manager – Immunology
Tel: +44.770.277.7378, scott.fleming@ucb.com

Michael Tuck-Sherman, Investor Relations, UCB
Tel: +32.2.559.9712,
michael.tuck-sherman@ucb.com

Antje Witte, Investor Relations, UCB
Tel: +32 2559 9414 / +49
2173481866, antje.witte@ucb.com

About Epratuzumab
Epratuzumab is a humanized anti-CD22 monoclonal antibody under investigation for the treatment of SLE. CD22 is a B-cell specific surface protein that is considered to be involved in B-cell function. The product was licensed from Immunomedics, Inc., Morris Plains, NJ, USA. Under the license agreement, UCB owns the rights and is responsible for the clinical development, and commercialization of epratuzumab in all autoimmune disorders including SLE.

About EMBLEM™
In EMBLEM™ (n = 227) patients were randomized to 1 of 6 intravenous regimens: placebo (PBO), epratuzumab cumulative dose (cd) 200, 800, 2400, or 3600 mg in equal divided doses using 2 every other week (EOW) infusions or epratuzumab cd 2400 mg delivered as 4 equal infusions 1 week apart. Concomitant oral corticosteroids (CS) and immunosuppressives (IS) were stable for at least 5 and 28 days, respectively, prior to first study drug infusion. Primary endpoint was responder rate on a combined index of clinical disease activity at week 12 (defined as reduction of all baseline (BL) BILAG 2004 A to B/C/D and BL BILAG B to C/D, no BILAG worsening in other organ systems, and no deterioration in SLEDAI or physician global assessment [VAS]), with no CS, IS and antimalarials increase over BL dose. The study was not powered to detect statistical differences between treatment arms.5

By week 12 (see table) combined responder index rates were higher in all epratuzumab groups than in the placebo group, reaching statistical significance in the epratuzumab 600mg weekly group (2400mg cumulative) and the combined group of all 74 patients who received a cumulative dose of 2400mg (600mg weekly and 1200mg every other week).

Dose regimen

PBO (n=38)

Emab cd 200mg

Emab cd 800mg

Emab cd 2400mg

Emab cd 3600mg

100mg EOW (n=39)

400mg EOW (n=38)

600mg weekly (n=37a)

1200mg EOW (n=37)

Combined group (n=74)

1800mg EOW (n=38)

Responders n (%)

8 (21.1)

12 (30.8)

10 (26.3)

17 (45.9)

15 (40.5)

32 (43.2)

9 (23.7)

Odds ratio (95%) vs placebo

1.7
(0.6-4.7)

1.3
(0.5-3.9)

3.2
(1.1-8.8)

P=0.03b

2.6
(0.9-7.1)

P=0.07 b

2.9
(1.2-7.1) p=0.02 b

1.2
(0.4-3.4)

Table - Combined responder index, week 12 (ITT population)

Emab = epratuzumab
a 2 patients randomized but never received drug
b p values not adjusted for multiple comparisons

Additionally, by Week 12, more patients in the epratuzumab 600mg weekly group, compared with placebo, had an improvement from BILAG A/B to BILAG D in the 6 body systems, indicating no active disease. A higher percentage of patients receiving epratuzumab 1200mg EOW, compared with placebo, had an improvement in baseline BILAG A/B scores to BILAG C or D in musculoskeletal, mucocutaneous, neuropsychiatric, and renal systems. In the cardiorespiratory system, all 7 patients in the epratuzumab 600mg weekly group had improved to a BILAG D at Week 12. Similarly, in the neuropsychiatric system, 5 out of 6 patients in the epratuzumab 600mg weekly group improved from BILAG B at baseline to BILAG D at Week 12.

About systemic lupus erythematosus (SLE)
SLE, commonly referred to as lupus, is a chronic and potentially fatal autoimmune disease with a variable and unpredictable course. Antibodies are generated against the body’s own nuclear proteins causing the immune system to attack its own cells and tissues resulting in inflammation and tissue damage. This can occur in any part of the body, but most often targets the heart, joints, skin, lungs, blood vessels, liver, kidneys and nervous system.

Lupus is characterized by periods of flares, or exacerbations, interspersed with periods of improvement or remission. The Lupus Foundation of America estimated that between 1.5-2 million Americans have a form of lupus, 90 percent of whom are women. Symptoms and diagnosis occur most often between the ages of 15 and 45. In the U.S., lupus is more common in African Americans, Latinos, Asians, and Native Americans than in Caucasians.

About UCB
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 3.2 billion in 2010. UCB is listed on Euronext Brussels (symbol: UCB).

About Immunomedics
Immunomedics (
NASDAQ: IMMU) is a New Jersey-based biopharmaceutical company primarily focused on the development of monoclonal antibody-based products for the targeted treatment of cancer, autoimmune and other serious diseases. Immunomedics has built a pipeline of therapeutic product candidates that utilize several different mechanisms of action. Immunomedics is developing epratuzumab for the therapy of B-cell hematopoietic tumors, such as non-Hodgkin lymphoma and acute lymphoblastic lymphoma.

Forward-looking statements - UCB
This press release contains forward-looking statements based on current plans, estimates and beliefs of management. Such statements are subject to risks and uncertainties that may cause actual results to be materially different 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, effects of future judicial decisions, changes in regulation, exchange rate fluctuations and hiring and retention of its employees.

Forward looking statements - Immunomedics
This release, in addition to historical information, may contain forward-looking statements made pursuant to the Private Securities Litigation Reform Act of 1995. Such statements, including statements regarding clinical trials, out-licensing arrangements (including the timing and amount of contingent payments), forecasts of future operating results, potential collaborations and capital raising activities, involve significant risks and uncertainties and actual results could differ materially from those expressed or implied herein. Factors that could cause such differences include, but are not limited to, risks associated with new product development (including clinical trials outcome and regulatory requirements/actions), our dependence on our licensing partners for the further development of epratuzumab for autoimmune indications and veltuzumab for non-cancer indications, competitive risks to marketed products and availability of required financing and other sources of funds on acceptable terms, if at all, as well as the risks discussed in the Company's filings with the Securities and Exchange Commission. The Company is not under any obligation, and the Company expressly disclaims any obligation, to update or alter any forward-looking statements, whether as a result of new information, future events or otherwise.

References

  1. Yee et al. Arthritis Rheum 2007;56:4113-9.
  2. Yee et al. Rheumatology (Oxford) 2009;48:691-5.
  3. FDA Systemic Lupus Erythematosus Working Group. Available at: www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM072063.pdf
  4. Wallace DJ et al. Evaluation of Treatment Success in Systemic Lupus Erythematosus Clinical Trials: Development of the British Isles Lupus Assessment Group-based Composite Lupus Assessment Endpoint. 2011 Arthrits Rheum 2011;63 (S10):S885
  5. Wallace DJ et al. Epratuzumab demonstrates clinically meaningful improvements in patients with moderate to severe systemic lupus erythematosus (SLE): Results from EMBLEM™, a Phase IIb study. .Arthritis Rheum 2010; 62 (S10):S605.

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