SuperGen Inc announced publication of results from three consecutive Phase II clinical trials of Dacogen (decitabine) for injection in patients with myelodysplastic syndromes (MDS), a company release said.
The combined Phase II trials enrolled 170 patients with intermediate and high-risk MDS. Investigators retrospectively analyzed the effect of low-dose Dacogen therapy on platelet response in 162 of the 170 patients. Platelets are a type of blood cell that prevents and stops bleeding. Seventy-eight per cent of the patients analyzed had low platelet counts associated with their MDS at baseline. All patients had an IPSS risk score of Intermediate I or higher.
Platelet responses occurred in 63 per cent of patients. Platelet responses occurred quickly and were usually (58%) observed after only one cycle of Dacogen. Furthermore, platelet response predicted for favourable overall survival (p<0.0001). The study concludes that Dacogen has a clinically significant, often long lasting, effect on the platelet count in a substantial number of high-risk MDS patients.
"This analysis provides additional clinical evidence that Dacogen might have a positive effect on survival outcome in MDS patients," said Karl Mettinger, chief medical officer and Senior VP. "These data demonstrate that Dacogen's clinical activity in MDS patients should be recognizable early in the treatment cycle, and will further support the Phase III data being submitted, as part of our rolling NDA for Dacogen, later this quarter," he added.
Decitabine has been shown to have a broad spectrum of activity in several haematological malignancies as well as solid tumours. Decitabine belongs to a new class of drugs called hypomethylating agents, with a unique mechanism of action. Methylation is a process in which methyl (CH3) groups are added to DNA to inactivate or "silence" genes.
Previously reported data from the randomized Phase III study of Dacogen in MDS patients demonstrated that adverse events observed were more common in patients receiving Dacogen than supportive care alone. These adverse events included leucopenia, febrile neutropenia, nausea, constipation, diarrhea, vomiting, pneumonia, arthralgia, headache and insomnia.
Currently, SuperGen is in the process of filing an NDA for Dacogen in MDS.
The principle investigator for these European studies was Professor Pierre W. Wijermans. The manuscript was published in the August 2004 issue of the journal Leukaemia Research.