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The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for the histone deacetylase (HDAC) inhibitor pracinostat to be used in combination with azacitidine to treat newly diagnosed acute myeloid leukemia (AML) patients who are 75 and older or unfit for intensive chemotherapy.
The FDA’s breakthrough designation is intended to expedite the development and review of new therapies for serious or life-threatening conditions.
To earn the designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.
The breakthrough therapy designation for pracinostat is supported by data from a phase 2 study of the HDAC inhibitor in combination with azacitidine in elderly patients with newly diagnosed AML who were not candidates for induction chemotherapy.
Detailed results from this trial were presented at the 20th Congress of the European Hematology Association last year. The research was sponsored by MEI Pharma, the company developing pracinostat.
The study included 50 AML patients who had a median age of 75 (range, 66-84).
The patients received pracinostat at 60 mg orally on days 1, 3, and 5 of each week for 21 days of each 28-day cycle. They received azacitidine subcutaneously or intravenously on days 1-7 or days 1-5 and 8-9 (per site preference) of each 28-day cycle.
According to updated data from MEI Pharma, the complete response rate was 42% (n=21), and the median overall survival was 19.1 months.
The company said these data compare favorably to a phase 3 study of azacitidine (AZA-AML-0011), which showed a median overall survival of 10.4 months with azacitidine alone and a complete response rate of 19.5% in a similar patient population.
The combination of pracinostat and azacitidine was thought to be well tolerated overall, with no unexpected toxicities. The most common grade 3-4 treatment-emergent adverse events included febrile neutropenia, thrombocytopenia, anemia, and fatigue.
