Research & Development
Sapacitabine is an oral nucleoside analogue prodrug that acts through a novel mechanism. The compound interferes with DNA synthesis by introducing single-strand DNA breaks leading to arrest of the cell division cycle at G2 phase and development of double-strand DNA breaks. Sapacitabine is currently being evaluated in a Phase 3 trial, SEAMLESS, in elderly AML under a SPA agreement with the U.S. Food and Drug Administration.
Both sapacitabine and its major metabolite, CNDAC, have demonstrated potent anti-tumor activity in blood and solid tumors in preclinical studies. In a liver metastatic mouse model, sapacitabine was shown to be superior to gemcitabine (Gemzar®; Lilly) or 5-FU, two widely used nucleoside analogues, in delaying the onset and growth of liver metastasis.
Cyclacel Pharmaceuticals has initiated a number of clinical trials to evaluate it's lead product candidate sapacitabine in both solid and hematological tumors laying the foundation for future Phase 2 and Phase 3 studies and combination studies with other anti-cancer agents. Over 300 patients have received sapacitabine in Phase 2 studies in AML, MDS, cutaneous T cell lymphoma (CTCL) and NSCLC. Sapacitabine has been administered to approximately 170 patients in five Phase 1 studies with both hematological malignancies and solid tumors. In December 2009 at the 51st Annual Meeting of the American Society of Hematology (ASH), Cyclacel Pharmaceuticals reported data from a randomized Phase 2 study including promising 1-year survival in elderly patients with AML aged 70 years or older.
Cyclacel Pharmaceuticals is conducting an ongoing, multicenter, Phase 1/2 clinical trial examining the safety and effectiveness of oral sapacitabine administered sequentially with decitabine. Interim results reported at ASCO 2011 included thirty-day mortality from all causes of 4.5% and 60-day mortality from all causes of 9.5%. The overall response rate was 34.8%.
Sapacitabine is currently being evaluated in Phase 2 trials in elderly patients with MDS, in non-small cell lung cancer (NSCLC) and chronic lymphocytic leukemia.
Cyclacel Pharmaceuticals reported 1-year survival data from a Phase 2 randomized trial of oral sapacitabine capsules in older patients with myelodysplastic syndromes (MDS) refractory to hypomethylating agents, such as azacitidine and decitabine at a poster presentation at the 52nd Annual Meeting of the American Society of Hematology (ASH) in Orlando, Florida.