Marrowforums - Ezatiostat HCL (TLK199 tablets) - A Novel glutathione analog prodrug for MDS

I came across this study titled 'Phase 1 multicenter dose-escalation study of ezatiostat hydrochloride (TLK199 tablets), a novel glutathione analog prodrug, in patients with myelodysplastic syndrome'. (This is the detailed PDF of the study and its results)

The conclusions were as follows -

Oral tablet formulation of TLK199 safe and well tolerated in patients with myelodysplastic syndromes (MDS)

Adverse effects primarily mild/moderate gastrointestinal events

Improvement in erythroid, neutrophil, and platelet cell lines observed after short-course dosing schedule

Responses accompanied by clinically meaningful improvement in patient symptoms

Majority of patients achieved decreased red blood cell (RBC) transfusion dependence

Findings support phase II development of TLK199 in extended dosing schedules

(Find the full article here)

According to the study, "Of the 23 patients who were RBC transfusion dependent, 8 (35%) achieved transfusion independence and 14 (61%) had a
reduction in the RBC transfusion requirements of 4 units/8 weeks (Table 5). One of 5 platelet transfusion–dependent patients achieved independence from platelet transfusions."

A Phase II study has been conducted too (given here). Here, "Telik Announces Positive Phase 2 Results of a Multicenter Study of Ezatiostat Hydrochloride (TELINTRA(R), TLK199) Tablets in Patients with Myelodysplastic Syndrome". Very interesting!

I also came across this case of "a 77 year old male who received less than two cycles of therapy with ezatiostat HCl which had to be aborted due to intolerable side effects, but which produced a sustained normalization of all three blood counts. This trilineage response has now lasted for more than a year. Interestingly, the patient began with a del(5q) abnormality and responded briefly to lenalidomide. Upon relapse of the anemia, a bone marrow showed the disappearance of the del(5q) but the appearance of a new clonal abnormality t(2;3)." (More details here).