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.
At ASCO 2012 Cyclacel reported interim data from three schedules of sapacitabine administered as single-agent treatment over a 4-week cycle in 63 patients with IPSS intermediate-1 or higher risk MDS after treatment failure of hypomethylating agents: 200 mg twice daily for 7 days as Arm G, 300 mg once daily for 7 days as Arm H, or 100 mg once daily for 5 days per week for 2 weeks as Arm I. Median overall survival was 240 days (approx. 8 months) for Arm G, 290 days (approx. 10 months) for Arm H, and 153 days (approx. 5 months) for Arm I. Median overall survival for all three arms is 252 days (approx. 8 months). In terms of secondary efficacy endpoints complete remissions (CRs) and major hematologic improvement (HI) in platelet counts or neutrophils, were observed on all 3 dosing schedules: 1 CR and 3 HIs in Arm G, 1 CR and 2 HIs in Arm H, and 2 CRs and 1 HI in Arm I. The 30-day mortality from all causes is 5%. Forty-one percent of all patients received 4 or more cycles. At the time of ASCO 2012 more than 34% of the patients were still alive and longer follow-up is needed to assess 1-year survival and overall survival.