Over 500 patients have received sapacitabine in Phase 2 studies in AML, MDS, CTCL and NSCLC and Phase 1 studies in both hematological malignancies and solid tumors. At the 2009 Annual Meeting of the American Society of Hematology (ASH), Cyclacel reported data from a randomized Phase 2, single-agent study of sapacitabine including promising 1-year survival in elderly patients with AML aged 70 years or older. At the 2011 Annual Meeting of the American Society of Clinical Oncology (ASCO), Cyclacel reported data from a pilot Phase 1/2 study including promising response rate, low 4-week and 8-week mortality in elderly patients with AML aged 70 years or older receiving sapacitabine alternating with decitabine. Cyclacel is currently enrolling patients in the SEAMLESS, Phase 3, randomized, registration-directed study of sapacitabine in elderly patients with acute myeloid leukemia (AML). The FDA and the European Medicines Agency have designated sapacitabine as an orphan drug for the treatment of both AML and MDS. Sapacitabine is part of Cyclacel's pipeline of small molecule drugs designed to target and stop uncontrolled cell division.
About sapacitabine in MDS
A total of 124 patients aged 60 years or older with MDS previously treated with hypomethylating agents (HMA) were treated in a Cyclacel Phase 2 study. Initially 61 patients were randomized across 3 dosing schedules of sapacitabine. Mature survival data from this cohort were presented at the 2010 Annual Meeting of the American Society of Hematology (ASH) on the basis of which the study was subsequently expanded to compare additional dosing schedules. Interim data on a further 63 patients were presented at the 2012 Annual Meeting of the American Society of Clinical Oncology (ASCO), with median survival of 8.4 months. This survival level is considered clinically significant by MDS experts in light of historical control expectations of 4 to 5 months. At the time of ASCO 2012 over 34% of the patients were still alive and longer follow-up is needed to assess 1-year survival and overall survival. Updated mature survival data will be reported in late 2012 or early 2013. Cyclacel is developing a pivotal development plan for the indication of second-line MDS to present to regulatory authorities.