Telik, Inc. reported positive interim data from a Phase 2 trial of its Telintra (TLK199) drug candidate in myelodysplastic syndrome (MDS). The data were reported in two presentations at the annual meeting of the American Society of Hematology in San Diego.
Hematologic Improvement Following Treatment with TLK199 (Telintra), a Novel Glutathione Analog Inhibitor of GST P1-1, in Myelodysplastic Syndrome: Interim Results of a Phase 2 Study (Abstract # 1428, Saturday, December 4, 2004):
A multicenter Phase 2 trial is ongoing to evaluate the safety and efficacy of Telintra in MDS patients. At the time of analysis, 34 MDS patients were evaluable for safety and 26 were evaluable for efficacy. Sixteen patients (61.5%) had clinically significant improvement in one or more blood cell lineages (red cells, white cells or platelets).
Clinically significant improvement was observed across all major MDS FAB subtypes (RA, RAEB, RAEB-t and RARS) and in all blood cell lineages. Using the International Working Group (IWG) MDS response criteria, 8 of 17 patients (47%) with white cell dysfunction had Hematologic Improvement -- Neutrophils (HI-N); 6 of 17 patients (35%) with platelet dysfunction had Hematologic Improvement -- Platelets (HI-P); and 8 of 24 patients (33%) with red blood cell dysfunction had Hematologic Improvement -- Erythrocytes (HI-E).
Three of 12 patients (25%) had trilineage improvement and four of 19 patients (21%) had bilineage improvement, meeting the IWG MDS objective response criteria for overall Hematologic Improvement (HI). Clinical responses were associated with decreased red blood cell, platelet and growth factor support requirements, in some cases leading to transfusion independence.
Telintra was well-tolerated in this predominantly elderly patient population (median age 74 years). Enrollment in the Phase 2 trial is continuing to evaluate alternative dose schedules.
TLK199 (Telintra), a Novel Glutathione Inhibitor of GST P1-1, Causes Proliferation and Maturation of Bone Marrow Precursor Cells and Correlates with Clinical Improvement in Myelodysplastic Syndrome Patients in a Phase 2 Study (Abstract # 2372, Sunday, December 5, 2004):
Telik scientists and academic collaborators reported translational data from the ongoing clinical trial demonstrating that Telintra stimulates the formation of bone marrow cells that are precursors to granulocytes and monocytes (white blood cells), erythrocytes (red blood cells) and platelets in MDS patients with abnormally low blood cell counts. These results correlated with clinical improvement.
Telintra is a novel small molecule that has been shown in preclinical testing to have myelorestorative activity in vitro and in vivo, when administered orally or by injection. It was discovered using Telik's proprietary TRAP small molecule drug discovery technology.
The myelodysplastic syndromes are a group of disorders characterized by the abnormal formation, development and maturation of blood elements. They are associated with a variable incidence of transformation to acute leukemia. The incidence and prevalence of MDS appears to be increasing, perhaps in part due to the aging of the population.