ZymoGenetics and Serono Present Positive Results of TACI-Ig Phase 1b Trial in Rheumatoid Arthritis at EULAR Meeting
Monday June 26, 1:00 am ET
Phase 2 Program to Start Later This Year
SEATTLE and GENEVA, June 26 /PRNewswire-FirstCall/ -- ZymoGenetics, Inc. (Nasdaq: ZGEN - News) and Serono (NYSE: SRA; virt-x: SEO) today announced favorable results from a Phase 1b clinical trial with TACI-Ig in 73 patients with rheumatoid arthritis (RA), recently presented at the 7th Annual European Congress of Rheumatology (EULAR). TACI-Ig is a soluble fusion protein that neutralizes molecules implicated in the pathogenesis of several autoimmune diseases. TACI-Ig appeared to be well tolerated across the full range of dose levels and schedules tested. Clear biologic effect was observed as patients showed schedule and dose dependent decreases in the levels of immunoglobulin (Ig) and serum rheumatoid factor levels. Although this study was not specifically designed to evaluate efficacy, encouraging trends were observed in ACR and DAS 28 scores, commonly used measurements of clinical benefit. Based on these promising results, ZymoGenetics and Serono expect to begin the Phase 2 clinical program of TACI-Ig in patients with RA in the second half of 2006.
In an oral presentation(1), Alain Munafo, Ph.D., Senior Scientific Director of Serono, reported that TACI-Ig appeared to be well tolerated in patients with moderate-to-severe RA. The most common adverse event was a generally mild injection site reaction affecting approximately 40% of the patients. There were no serious adverse events reported. No patients formed detectable antibodies to TACI-Ig, and the patients' vaccination immune status did not appear to be compromised by the drug.
TACI-Ig demonstrated clear biological activity, with schedule and dose-dependent reductions of immunoglobulin levels in line with the proposed mechanism of action. In a cohort that received seven doses of TACI-Ig over a three-month period, patients showed:
-- Reductions of several biomarkers typically found in RA patients,
including:
- IgM, IgA and IgG reductions of 54%, 37% and 21% respectively;
- Reduction of peripheral blood B-cell levels with a maximum decrease
of 30-40%
- 40-45% reduction of IgM-RF, IgA-RF and IgG-RF
-- Trends toward improvement of the ACR and DAS 28 scores commonly used to
measure disease severity and effects of treatment.
In a separate poster presentation(2), Ivan Nestorov, Ph.D., Scientific Fellow of ZymoGenetics, reported that there was a well-defined relationship between TACI-Ig exposure and immunoglobulin response. IgM levels were found to be the most responsive to TACI-Ig exposure, followed respectively by IgA and IgG levels. Dosing frequency seemed to play as important a role as dose level in the response of the three biomarkers.
The primary objective of the Phase 1b study was to determine the safety and tolerability of TACI-Ig in RA patients and to examine the relationship between TACI-Ig dose and schedule with markers of biologic and disease activity. The trial enrolled adult male and female patients with active, moderate-to-severe RA. Patients received single or multiple doses of either TACI-Ig or placebo for a maximum period of three months.
Abstracts
The abstracts and presentation slides are available at www.zymogenetics.com in the "What's New" section on the home page.
Background material
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About TACI-Ig
ZymoGenetics and Serono are developing TACI-Ig for the treatment of autoimmune diseases and B-cell malignancies. TACI-Ig is a soluble receptor that binds to BLyS and APRIL, TNF family cytokines that promote B-cell survival and the production of harmful autoantibodies, which cause certain autoimmune diseases such as systemic lupus erythematosus (SLE). Current data indicates that levels of BLyS and APRIL are elevated in patients with rheumatoid arthritis, SLE and B-cell malignancies. TACI-Ig has been shown to affect several stages of B-cell development and may inhibit the survival of cells responsible for making antibodies. ZymoGenetics is developing TACI-Ig in collaboration with Serono S.A. and is conducting clinical studies in patients with SLE, rheumatoid arthritis and advanced B-cell malignancies, such as multiple myeloma, B-cell non-Hodgkin's lymphoma and chronic lymphocytic leukemia. Commencing July 1, TACI-Ig will be referred to by its International Nonproprietary Name "atacicept." |
