Pharmion Corporation announced that it has submitted a New Drug Application (NDA) to the US Food and Drug Administration (FDA) for approval to market Vidaza (azacitidine for injectable suspension) as a treatment for Myelodysplastic Syndromes (MDS). Vidaza has been granted fast-track status by the FDA based on its potential to treat a serious, life threatening condition and address an unmet medical need.
Vidaza has been granted orphan product designation by the FDA for the MDS indication, which, if approved, entitles the drug to seven years of market exclusivity for the indication in the US.
"The submission of this NDA represents a significant milestone for Pharmion," said Patrick J Mahaffy, Pharmion's president and CEO. "We are proud that our work with Cancer and Leukemia Group B (CALGB) and the National Cancer Institute (NCI) has developed this product."
The NDA submission is based upon an NCI-sponsored Phase III study for the treatment of MDS conducted by CALGB and two supportive Phase II CALGB studies, which were also sponsored by NCI. The randomized controlled Phase III study included 191 patients comparing the effects of Vidaza plus best supportive care versus best supportive care alone as a treatment of MDS. The results of this study were published in the May 2002 Journal of Clinical Oncology.
"It is gratifying to see data from these CALGB clinical trials form the basis of this NDA submission for azacitidine," said Dr Richard L Schilsky, professor of medicine and associate dean for clinical research at the University of Chicago and chairman of the CALGB. "We have been pleased to work with Pharmion to validate the published results from these studies."
The NDA was submitted under Subpart H of the NDA regulations, under which a drug can be approved based on either evidence from adequate and well-controlled studies of the drug's effect on a surrogate endpoint that reasonably suggests clinical benefits or of the drug's effect on a clinical endpoint other than survival, conditioned upon the sponsor agreeing to complete a confirmatory study.
In September 2003, Pharmion initiated a confirmatory clinical trial comparing the effect of Vidaza to conventional care options on survival in MDS patients. The study, which will examine survival outcomes as well as secondary endpoints, will recruit over 350 patients from treatment centers across the U.S., Europe and Australia and will be one of the largest studies to date in this disease.
In addition to its cytotoxic effects, azacitidine is a member of a class of drugs in development known as "hypomethylating" or "demethylating" agents. Methylation of DNA is a major mechanism regulating gene expression. Researchers have determined that an increase in methylation of DNA can result in blockage of the activity of genes that regulate cell division and differentiation, known as "suppressor genes." With suppressor gene expression blocked, cell division becomes unregulated, causing or promoting cancer. In studies, researchers have demonstrated that azacitidine can reverse the methylation of DNA, leading to reexpression of suppressor genes and a resulting differentiation and maturation of cells.
MDS is a bone marrow disorder characterized by the production of abnormally functioning, immature blood cells. The highest prevalence of MDS is in patients over 60 years of age. According to the American Cancer Society, there are an estimated 10,000-20,000 new cases of MDS in the United States each year. Survival rates range from six months to six years for the different types of MDS. MDS can result in death from bleeding and infection in the majority of patients, and transformation to acute myelogenous leukemia (AML) occurs in up to 40 per cent of high-risk patients. The prognosis for patients transforming to AML is exceptionally poor.
Pharmion is focused on acquiring, developing and commercializing innovative products for the treatment of hematology and oncology patients in the US, Europe and additional international markets.