PALO ALTO, Calif., Dec. 12, 2012 /PRNewswire/ -- Telik, Inc. (Nasdaq: TELK) announced today the publication of a clinical trial abstract in the proceedings of the 54 th Annual Meeting of the American Society of Hematology in Atlanta, Georgia. The abstract, " Oral Ezatiostat HCl (Telintra), a Glutathione Analog Prodrug GSTP1-1 Inhibitor, for Treatment of Patients with Myeloid Growth Factor-Resistant Idiopathic Chronic Neutropenia (ICN)," by Roger M. Lyons, MD; Sharon T. Wilks, MD; and of David J. Friedman MD, PhD, of Cancer Care Centers of South Texas, US Oncology in San Antonio, Texas; and Shelby A. Young, RN, BSN, and Gail L. Brown, MD, of Telik, Inc., in Palo Alto, California, is available online at Blood (ASH Annual Meeting Abstracts) 2012 120: Abstract 4394.
This abstract reports the preliminary results of a clinical trial with ezatiostat to study the treatment of patients with idiopathic chronic neutropenia (ICN). ICN is a rare group of blood disorders characterized by low circulating neutrophils, recurrent fevers, mucosal inflammation and serious systemic infections. The risk and severity of these complications is related to abnormally low levels of white blood cells. Most patients initially respond to treatment with granulocyte colony stimulating factors (G‑CSF); however, some patients fail to respond or become resistant to G‑CSF treatments. Further, G‑CSF therapy is often associated with bone and muscle pain, low platelet counts and enlargement of the spleen. Patients may need to be on G‑CSF for the rest of their lives, and these side effects can interfere with therapy.
Ezatiostat is an investigational agent in development for the treatment of ICN. The compound is a glutathione S-transferase (GST) inhibitor that activates Jun kinase, which has been demonstrated to promote growth and maturation of hematopoietic progenitors. Four patients with longstanding, severe ICN and inadequate absolute neutrophil count (ANC) response to G‑CSF were enrolled in this phase 2 trial. These patients all had a history of frequent hospitalization for sepsis, prolonged courses of antibiotics and poor response to myeloid growth factors, including G‑CSF. The patients were treated with orally administered ezatiostat.Ezatiostat treatment of these ICN patients with grade 4 neutropenia who were not responsive to G‑CSF resulted in a durable increase in their white-blood-cell levels, leading to clinically significant reductions in serious infections. Extended oral treatment with ezatiostat has been well tolerated in these patients and may be appropriate for longer-term therapy. Ezatiostat is the first targeted GSTP1-1 inhibitor that has been shown to have a positive effect on white blood cell levels in ICN and may provide molecular insight into the pathophysiology of ICN. These results suggest that further study is warranted of ezatiostat's potential role as an oral therapy alternative or adjunct to G‑CSF in the treatment of ICN in patients who are not responsive to G‑CSF.
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