ZymoGenetics and Serono Report Detailed Positive Results From Atacicept Phase 1b Clinical Trial in Patients With Lupus
Monday November 13, 1:00 am ET
Clear biologic activity, tolerability and trends toward efficacy observed
SEATTLE and GENEVA, Nov. 13 /PRNewswire-FirstCall/ -- ZymoGenetics, Inc. (Nasdaq: ZGEN - News) and Serono (virt-x: SEO and NYSE: SRA) today presented positive results at the American College of Rheumatology (ACR) annual meeting from a Phase 1b study in systemic lupus erythematosus (SLE) patients treated with atacicept(1). The results showed that atacicept was well tolerated across all dose levels and schedules in the study. In addition, atacicept therapy was associated with clear biologic activity, as shown by dose-dependent reductions in several biologic markers, consistent with atacicept's proposed mechanism of action.
"ZymoGenetics and Serono are striving to develop an effective therapy for patients who suffer from lupus," said Bruce L.A. Carter, President and Chief Executive Officer of ZymoGenetics. "We believe atacicept has the potential to help people with this debilitating disease."
The primary objective of the dose-escalating Phase 1b clinical trial, which included 49 patients with SLE in 6 cohorts, was to determine the safety and tolerability of atacicept administered subcutaneously. Secondary objectives included examining the effects of various dose and schedule regimens on markers of biologic activity and disease activity.
"The Phase 1b results are very encouraging and we are looking forward to moving the clinical development of atacicept in patients with SLE to Phase 2," said Franck Latrille, Senior Executive Vice President, Corporate Global Product Development at Serono.
ZymoGenetics and Serono are in dialogue with the FDA regarding the SLE Phase 2 clinical development program. The companies are planning to initiate the trial in SLE in mid-2007.
Key Study Findings:
Clear biologic activity:
Consistent with the mode of action:
-- Immunoglobulins showed prompt dose-related decreases with atacicept
treatment.
-- Among patients treated with the highest study dose of atacicept
(9mg/kg), median IgA, IgG and IgM levels were reduced by 32, 16 and
nearly 50 percent relative to baseline. Patients treated with
placebo showed average reductions of only four percent.
-- Repeated doses were associated with greater decreases in
immunoglobulin (Ig) levels than single equivalent doses.
-- Following treatment cessation, Ig levels returned towards baseline.
-- Mature and total B-cells showed a sustained, dose-related reduction.
Tolerability:
-- No serious adverse events were reported in patients treated with
atacicept.
-- There was no evidence of increased infection risk among treated
subjects, and no binding antibodies to atacicept were detected.
Positive trend towards efficacy:
-- Although the study was not designed to evaluate efficacy, compared to
placebo an overall positive trend in SELENA-SLEDAI scores(2) and
complement levels was seen in patients treated with multiple doses of
atacicept.
A separate poster(3) presented at ACR reviewed findings from a Phase 1b study with atacicept in patients with rheumatoid arthritis, as announced earlier this year. The companies are planning to initiate the Phase 2 study with atacicept in RA patients before the end of 2006.
About the Study
The double blind, placebo-controlled, dose escalating, multi-site Phase 1b trial enrolled forty-nine patients with mild-to-moderate SLE. Six cohorts, consisting of eight patients each, were treated with either atacicept or placebo. Cohorts 1 through 4 received a single subcutaneous dose of 0.3, 1, 3, or 9 mg/kg of atacicept respectively. Cohorts 5 and 6 received four weekly doses of 1 mg/kg or 3 mg/kg respectively. Patients were followed for either six weeks (cohorts 1-4) or nine weeks (cohorts 5-6). All patients were monitored during and for several weeks after dosing for safety purposes.
The primary outcome measure was the systemic and local tolerability of atacicept administered subcutaneously. The secondary measures included pharmacokinetics and pharmacodynamics, as well as measures of SLE disease activity.
Atacicept was well tolerated by patients with SLE at all doses investigated. There was a clear demonstration of biologic activity consistent with the mechanism of action of atacicept and positive trends towards efficacy were observed.
Overall, the results demonstrated a favorable tolerability profile. The predominant adverse event noted was a mild to moderate local injection site reaction (redness of skin or pain at the injection site), which was observed in 50% of atacicept subjects and less frequently in the placebo and 0.3 mg/kg groups. Few notable differences were observed between atacicept and placebo in the nature, severity or frequency of adverse events.
About Atacicept
ZymoGenetics and Serono are developing atacicept (formerly referred to as TACI-Ig) for the treatment of autoimmune diseases and B-cell malignancies. Atacicept contains the soluble TACI receptor that binds to the cytokines BLyS and APRIL. These cytokines, in turn, are members of the tumor necrosis factor (TNF) family that promote B-cell survival and autoantibody production associated with 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. Atacicept has been shown to affect several stages of B-cell development and may inhibit the survival of cells responsible for making antibodies.
Posters
The abstracts and posters are available at www.zymogenetics.com in the 'What's New' section on the home page.
Background material
For free B-roll, video and other content for Serono and its products, please visit the Serono Media Center www.thenewsmarket.com/Serono. You can download print-quality images and receive broadcast-standard video digitally or by tape from this site. Registration and video is free to the media. |
