FDA Grants Venclexta an Accelerated Approval for AML Treatment

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A Venclexta combination was granted an accelerated approval to treat older patients with acute myeloid leukemia who are ineligible for chemotherapy.

The Food and Drug Administration (FDA) granted an accelerated approved to Venclexta (venetoclax) in combination with azacytidine, decitabine or low-dose cytarabine (LDAC) to treat patients with acute myeloid leukemia (AML) who are at least 75 years old and/or are ineligible for chemotherapy.

“AML is an extremely aggressive and debilitating blood cancer, and outcomes for patients ineligible for intensive chemotherapy are very poor,” said Michael Severino, M.D., executive vice president of research and development and chief scientific officer, AbbVie — one of the co-manufacturers of the drug – in a statement. “This new approval for Venclexta marks a significant milestone for AbbVie and, more importantly, for patients diagnosed with this deadly disease. We look forward to continuing our work developing Venclexta and advancing treatment options in other aggressive cancers."

The approval is based on two phase 1b/2 trials in this setting: the M14-358 study and the M14-387 study.

The phase 1b open-label dose escalation and expansion M14-358 study included treatment-naïve patients with AML aged 60 years or older who were not fit to receive intensive chemotherapy. Patients received Venclexta in combination with a hypomethylating agent (azacitidine or decitabine). Key outcome measures for the trial included complete remission/complete remission with partial hematological recovery (CRh), overall survival and safety.

Combining Venclexta with azacitidine led to a complete remission rate of 37 percent and a CRh rate of 24 percent. The rates were 54 percent and 7.7 percent, respectively, with the combination of Venclexta and decitabine. Grade 3/4 side effects included anemia, low platelet count, decreased potassium levels, low white blood cell count with fever and low white blood cell count.

The open-label phase 1b/2 dose escalation and expansion M14-387 study included previously untreated patients 60 years or older who were unfit to receive intensive chemotherapy. Patients received Venclexta in combination with low-dose cytarabine. The main study endpoints were complete remission/CRh, objective response rate, overall survival and safety.

The complete remission and CRh rates with the combination were both 21 percent. Grade 3/4 side effects included sepsis, decreased phosphate levels, high blood pressure, decreased potassium levels, pneumonia and low white blood cell count with fever.

This is not the first accelerated approval that the drug has received. In 2016, the FDA granted Venclexta an accelerated approval for previously treated patients with chronic lymphocytic leukemia (CLL) who have a 17p deletion. The accelerated approval led to a full approval in June 2018 for patients with CLL or small lymphocytic leukemia (SLL), regardless of 17p deletion. At the same time, the FDA also approved the agent to be used in combination with Rituxan (rituximab).

“Many people with acute myeloid leukemia are unable to tolerate standard intensive chemotherapy, and the Venclexta combination regimens represent important new options for these patients,” said Sandra Horning, chief medical officer at Genentech, a unit of Roche, the other co-manufacturer of the drug.

The accelerated approval of venetoclax in AML is contingent on the results of a confirmatory trial.