Epratuzumab reduces SLE disease activity in phase IIB EMBLEM study

Nov 10 2010

• Epratuzumab reduced disease activity in adult patients with moderate to severe active systemic lupus erythematosus (SLE)
• Reduced disease activity observed as early as week 8, with further improvements to week 12

UCB (EURONEXT:UCB) and U.S. based partner Immunomedics Inc. (Nasdaq:IMMU) announced that results from the phase IIB study, EMBLEM™, showed that certain doses of epratuzumab were associated with a meaningful and statistically significant reduction in disease activity in adult patients with moderate to severe active SLE.

The EMBLEM™ study was designed to evaluate the efficacy and safety of epratuzumab (in combination with immunosuppressants) in SLE, identify an optimal dose and regimen for further studies, and validate and analyze the performance of a new composite efficacy endpoint.

The data, which were presented today in Atlanta at the 74th Annual Scientific Meeting of the American College of Rheumatology (ACR), demonstrated that, in EMBLEM™, all epratuzumab doses, which ranged from 200mg to 3600mg cumulative dose administered during one 12-week treatment cycle had numerically superior response rates compared to placebo at week 12. For patients receiving epratuzumab at a cumulative dose of 2400mg, there were meaningful and statistically significant reductions in SLE disease activity, with responder rates more than double those of placebo.

Epratuzumab was associated with a similar incidence of serious adverse events (including infections) and infusion reactions compared to placebo.

"While medical advances have improved the lives and survival of people with lupus, effective therapeutic options remain limited.  Given these positive results, we remain excited with the future potential of epratuzumab." commented lead study investigator Daniel J. Wallace, M.D., Clinical Professor of Medicine, David Geffen School of Medicine, UCLA.

Additionally, based on analysis of improvement in BILAG 2004 by body system in EMBLEM™, most patients had symptom reduction or absence of active disease within specific body systems after treatment with epratuzumab. Improvements were particularly prominent in cardiorespiratory and neuropsychiatric systems in which symptom improvements are often difficult to achieve.

These results demonstrated that in a patient population with predominantly high or severe disease activity, differences in responder rates between the epratuzumab 600mg weekly and 1200mg every other week groups, and the placebo group was observed as early as week 12, with the emergence of improvements apparent in week 8.

In two previous phase II randomized controlled trials epratuzumab treatment resulted in clinically meaningful reduced disease activity, improved health-related quality of life (HRQoL) measurements and reduced reliance on corticosteroids compared to placebo treatment in patients with active moderate and severe SLE.

"We are pleased by the repeated consistency of symptom improvement demonstrated by epratuzumab in all our clinical studies to date and we look forward to confirming these results in our phase 3 studies due to start later this year," said Prof. Dr. Iris Loew-Friedrich, Chief Medical Officer of UCB.  She added, "Achieving a BILAG improvement, especially at an early timepoint seen in EMBLEM™, is a hopeful sign of the drug's future potential."

Epratuzumab is a humanized monoclonal antibody targeting CD22 and modulating B-cell activity. 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.

Source UCB and Immunomedics Inc.