The FDA has granted breakthrough therapy status for the investigational drug pracinostat (MEI Pharma) in combination with azacitidine (Vidaza, Celgene) for the treatment of patients with newly diagnosed acute myeloid leukemia (AML) who are 75 years of age or older, or who are unfit for intensive chemotherapy. In addition, Celgene has reached agreement with the FDA on a proposed phase 3 study design.
A breakthrough therapy designation is intended to expedite the development and review of drugs for serious or life-threatening conditions.
Pracinostat is an oral inhibitor of a group of enzymes called histone deacetylases (HDACs). HDACs belong to a larger set of proteins collectively known as epigenetic regulators that can alter gene expression by chemically modifying DNA or its associated chromosomal proteins. Abnormal activity of these regulators is believed to play an important role in cancer and other diseases.
The FDA’s breakthrough therapy designation was supported by data from a phase 2 study of pracinostat plus azacitidine in elderly patients with newly diagnosed AML who were not candidates for induction chemotherapy. The results showed median overall survival (OS) of 19.1 months and a complete response (CR) rate of 42% (21 of 50 patients). These data compared favorably with those of a phase 3 study of azacitidine, which showed median overall survival of 10.4 months with azacitidine alone and a CR rate of 19.5% in a similar patient population. The combination of pracinostat and azacitidine was generally well tolerated, with no unexpected toxicities. The most common grade-3 or grade-4 treatment-emergent adverse events included febrile neutropenia, thrombocytopenia, anemia, and fatigue.
AML is the most common acute leukemia affecting adults, and its incidence is expected to continue to increase as the population ages. The American Cancer Society estimates that approximately 20,830 new cases of AML occur each year in the United States in individuals with an average age of approximately 67 years. Treatment options for AML have remained virtually unchanged for nearly 40 years. Front-line treatment consists primarily of chemotherapy. The National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology recommend the hypomethylating agent azacitidine or decitabine as low-intensity treatment options for AML patients older than 60 years of age who are unsuitable for induction therapy.
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