The MDS Beacon™

Interim results from an ongoing Phase 2 study show that sapacitabine produces a response at three different dosing levels in myelodysplastic syndromes (MDS) patients.  The findings were presented as a poster at the American Society of Hematology 2009 annual meeting on December 5.

Sapacitabine is an orally-administered drug that mimics naturally-occurring chemical structures in the body and helps stop abnormal cell division that is characteristic of MDS or acute myeloid leukemia (AML). It is currently being investigated for the treatment of MDS and AML.

The primary goal of the ongoing Phase 2 trial is to evaluate the one-year survival rate in MDS patients. Researchers also have designed the trial to test different dosing schedules of sapacitabine. In case participants respond to all dosing schedules, researchers want to determine which one produces the best one-year survival rate.

The study participants were required to be more than 60 years old with intermediate-2 or high-risk MDS subtypes, and they must already have been treated with – and no longer be responding to – either Dacogen (decitabine) or Vidaza (azacitidine).

The participants have been divided into three groups receiving three different doses of sapacitabine.  The first group has received 200 mg sapacitabine twice a day for seven consecutive days every three to four weeks. The second group has received 300 mg twice a day for seven consecutive days every three to four weeks.  The third group has received 400 mg twice a day for three days per week for two weeks, within an overall three- to four-week cycle.  There is no maximum limit of cycles, but treatment with sapacitabine is halted if a patient shows signs of excessive toxicity.

Across all three groups, sapacitabine thus far has had an overall response rate of 23 percent.  The 23 percent overall response rate consists of one patient (2.6 percent) who achieved a complete response, and eight patients (20.5 percent) who registered major hematological improvements.

The second group of patients had the highest overall response rate (38 percent), compared to the first group (23 percent) and the third group (8 percent).  The median time to response was one to two cycles.

Common side effects included fatigue, nausea, diarrhea, and constipation.  Patients also experienced varying degrees of low white blood cell or red blood cell counts.  One patient died due to causes unrelated to treatment with sapacitabine.

Researchers concluded that all three dosing regimens of sapacitabine are safe for treating MDS.  Based on the preliminary results, they believe the second group’s dose (300 mg for seven consecutive days every three to four weeks) is the most effective regimen.

Cyclacel, the manufacturer of sapacitabine, is currently still recruiting MDS patients for the above trial to further evaluate the efficacy, safety, and optimal dosing of sapacitabine.

For more information, please see abstract 1758 at the American Society of Hematology Web site or Cyclacel’s related press release.