Telik Inc. announced positive results from its Phase 2 trial of Telintra (ezatiostat hydrochloride tablets, TLK199) in myelodysplastic syndrome (MDS) patients with an International Prognostic System Score (IPSS) of low to intermediate-1 risk. Eighty-seven patients were randomized and treated at 23 investigational sites. The primary objective of the study was to determine the Hematologic Improvement (HI) rate according to the International Working Group criteria (IWG, 2006). After initial dose ranging in 14 patients, two dose levels were selected for further study. Subsequently, 37 patients were treated at 3 gm daily for two weeks followed by a one week rest period, and 36 patients were treated at 2 gm daily for three weeks followed by a one week rest period.
The overall Hematologic Improvement – Erythroid (HI-E) rate was 22%, 13 of 60 evaluable patients, (95% CI, 12.1-34.2). The median duration of HI-E response was 46 weeks (range 2-51). In responders, the median hemoglobin level was seen to increase by 2.0 gm/dL. Eleven of 38 red blood cell (RBC) transfusion-dependent patients (29%) had clinically significant RBC transfusion reductions (reduction of 4U/8 weeks, IWG 2006) with 4 patients (11%) achieving RBC transfusion independence and 3 patients continuing on treatment. In addition, one patient continues in remission for more than 12 months following discontinuation of therapy.
Telintra inhibits the enzyme glutathione S-transferase P1-1, which may activate JNK kinase, a key regulator of cellular growth and differentiation of blood precursor cells. Telintra has been shown to stimulate normal multilineage differentiation of blood stem cell precursors and induce cancer cell death, or apoptosis, in human leukemia cell lines.
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