Image by Lance Liotta
The US Food and Drug Administration (FDA) has granted a third breakthrough therapy designation for the BCL-2 inhibitor venetoclax (ABT-199).
This time, the designation is for venetoclax in combination with hypomethylating agents to treat patients with treatment-naïve acute myeloid leukemia (AML) who are ineligible for standard induction therapy.
Venetoclax previously received breakthrough designation as a single agent for patients with relapsed or refractory chronic lymphocytic leukemia (CLL) and in combination with rituximab to treat patients with relapsed or refractory CLL and 17p deletion.
Breakthrough therapy designation is designed to accelerate the development and review of medicines that demonstrate early clinical evidence of a substantial improvement over current treatment options for serious diseases.
Venetoclax is currently under investigation in a phase 1/2 trial in combination with low-dose cytarabine for treatment-naïve patients with AML and in a phase 1b study in combination with decitabine or azacitidine for treatment-naïve AML patients.
A phase 2 study of single-agent venetoclax in AML has been completed. The results were presented at ASH 2014.
At that time, the trial had enrolled 32 patients, 30 of whom had relapsed or refractory disease. Patients had a median age of 71 (range, 19 to 84), and half were male.
The overall response rate was 15.5%, with 1 patient achieving a complete response (CR) and 4 patients achieving a CR with incomplete count recovery (CRi).
The researchers noted that 3 of the patients who had a CR/CRi had IDH mutations. Two of these patients also achieved minimal residual disease negativity.
The median bone marrow blast count in evaluable patients decreased 36% after treatment, and 6 patients (19%) had at least a 50% reduction in bone marrow blasts.
Common adverse events following treatment (occurring in at least 25% of patients) included nausea, diarrhea, fatigue, neutropenia, and vomiting.
Grade 3 and 4 adverse events (occurring in 3 or more patients) included febrile neutropenia, anemia, and pneumonia. No patient died as a result of treatment-related adverse events.
Venetoclax is being developed by AbbVie in partnership with Genentech and Roche.
