AbbVie’s FDA application for venetoclax in acute myeloid leukemia

AbbVie has submitted a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) for venetoclax in combination with a hypomethylating agent (HMA) or in combination with low-dose cytarabine (LDAC) for the treatment of newly diagnosed patients with acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy.

The sNDA submission is based on investigational data from two studies: M14-358, a Phase 1b trial evaluating venetoclax in combination with an HMA (azacitidine or decitabine), and M14-387, a Phase 1/2 trial of venetoclax in combination with LDAC.

AML, primarily a disease of older patients, is the most common form of acute leukemia in adults, in which the bone marrow makes abnormal, immature types of white blood cells, red blood cells or platelets. AML is an aggressive blood cancer that, if left untreated, can progress quickly.

Approximately 27 percent of patients diagnosed with AML will survive five years or more. Disease recurrence occurs in most patients with AML within three years of diagnosis. Although few treatments are available, AML patients who are ineligible for intensive remission induction therapy may be treated with LDAC or HMAs. Only about one-third of AML patients older than age 60 are able to tolerate the intensive chemotherapy required to achieve optimal results.

Venetoclax, an oral B-cell lymphoma-2 (BCL-2) inhibitor, has been granted four Breakthrough Therapy Designations (BTDs) from the FDA including for the combination of venetoclax with an HMA (azacitidine or decitabine) for treatment-naïve patients with AML who are ineligible to receive standard induction therapy (high-dose chemotherapy) and for the combination of venetoclax with LDAC for treatment-naïve patients with AML who are ineligible for intensive chemotherapy.

If approved in AML, venetoclax would be available for use in two blood cancers, chronic lymphocytic leukemia (CLL) and AML.

In addition to CLL and AML, venetoclax is being studied in a range of hematologic malignancies including multiple myeloma (MM), non-Hodgkin lymphoma (NHL) and myelodysplastic syndrome (MDS).

Michael Severino, M.D., executive vice president of research and development and chief scientific officer, AbbVie said, “The data submitted to the FDA may potentially reshape how AML is treated. We look forward to working with the FDA and other health authorities during the review of these data.