Pharmion Corporation has announced top line results from the multi-institutional, international, randomised, phase III controlled trial of Vidaza (azacitidine for injection) versus conventional care regimens (CCR) in the treatment of patients with higher-risk myelodysplastic syndromes (MDS). In the primary endpoint analysis, Vidaza treatment was associated with a median survival of 24.4 months versus 15 months for those receiving CCR treatment, an improvement of 9.4 months with a stratified log-rank p-value of 0.0001.
The hazard ratio describing this treatment effect was 0.58 (95 per cent confidence interval of 0.43 to 0.77). Two-year survival rates were 50.8 per cent versus 26.2 per cent for patients receiving Vidaza versus CCR. Median number of treatment cycles was nine for Vidaza.
The survival benefits of Vidaza were consistent regardless of the CCR treatment option (best supportive care (BSC) alone, low-dose cytarabine plus BSC or standard chemotherapy plus BSC) utilized in the control arm.
"These landmark results, showing a significant improvement in survival in the most advanced MDS patients, validate the benefit Vidaza can provide patients with this extremely difficult to treat disease," said Dr Lewis R Silverman, associate professor of Medicine, Division of Haematology and Medical Oncology, Mount Sinai School of Medicine. "Building on the established data from our earlier clinical studies, which showed that Vidaza offers transfusion independence to many patients with MDS, we now see that Vidaza not only improves a patient's life, but extends it as well."
"With these very exciting results for Vidaza, survival should now be the standard by which we evaluate treatment options for higher-risk MDS," said Dr. Alan F List, Chief, Malignant Haematology Division and Deputy Physician in Chief, H Lee Moffitt Cancer Centre and Research Institute. "Importantly, as the first and only epigenetic therapy to have demonstrated a survival benefit in any cancer, these findings should accelerate exploration of Vidaza in other malignancies where hypermethylation is believed to play a key role in tumour development and progression."
"We are extremely gratified with the results from the Vidaza Survival Study, which for the first time bring the hope of prolonged survival for patients with higher-risk MDS," said Patrick J Mahaffy, Pharmion's chief executive officer and president. "As the only therapy to have ever demonstrated a survival advantage in MDS, and especially to have demonstrated an improvement of this magnitude, Vidaza is unique in the treatment for this disease."
Pharmion expects to present full study results at an upcoming medical meeting. Based on these results, Pharmion intends to file a Marketing Authorization Application (MAA) in the European Union (EU) for Vidaza for the treatment of higher-risk MDS before the end of this year and will shortly thereafter submit additional international regulatory submissions. The company will also file a supplemental New Drug Application (NDA) with the US Food and Drug Administration (FDA) to include these data in the prescribing information in the US.
Pharmion is also developing a next generation product, oral Azacitidine, for the treatment of MDS and other cancers where demethylation can provide an anti-tumour effect. Oral Azacitidine is the subject of a phase I multi-centre, open label dose escalation trial that will assess the maximum tolerated dose, dose limiting toxicities and safety of a seven day, multi-cycle oral dosing regimen of oral Azacitidine in patients with MDS and AML. In addition, the trial will examine pharmacokinetics and pharmacodynamic effects of orally administered Azacitidine, as compared with parenteral Vidaza.