sNDA Submitted to FDA for Venetoclax in AML Patients Ineligible for Intensive Chemotherapy

AbbVie has submitted a supplemental new drug application (sNDA) to the US Food and Drug Administration (FDA) for venetoclax to be used in combination with a hypomethylating agent (HMA) or low-dose cytarabine (LDAC) for the treatment of patients with acute myeloid leukemia (AML) who are not eligible to undergo intensive chemotherapy.

“AML is an especially lethal and aggressive form of blood cancer with limited advances in care in 3 decades and few treatment options for patients ineligible for intensive chemotherapy,” AbbVie’s executive vice president of research and development and chief scientific officer Michael Severino, MD, said in a recent statement. “The data submitted to the FDA may potentially reshape how AML is treated.”

Described as an oral B-cell lymphoma-2 (BCL-2) inhibitor, venetoclax, was designed to target the protein BCL-2. Patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) could have an increase in BCL-2, which hinders cancer cells from naturally self-destructing. By targeting BCL-2, venetoclax works to restore the process of apoptosis.

The decision to submit the sNDA was based off of promising findings yielded from 2 recent studies: a phase 1b trial, referred to as M14-358, which assessed the drug in combination with an HMA (either azacytidine or decitabine), and a phase 1/2 trial, called M14-387, which evaluated the drug in combination with LDAC.

About 27% of patients diagnosed with AML are estimated to have a survival of 5 years or longer; however, recurrence is estimated to occur in the majority of these patients within 3 years’ time. Patients who are not eligible to undergo intensive remission induction therapy have the potential to be treated with LDAC or HMAs. There are many challenges associated with the treatment of AML, leaving a large, unmet medical need.

Previous to this, venetoclax has already been granted 4 breakthrough therapy designations including: venetoclax in combination with an HMA for treatment-naïve patients with AML not eligible to receive standard induction therapy and venetoclax in combination with LDAC for treatment-naïve patients with AML ineligible for intensive chemotherapy.

Furthermore, recently, the drug was granted expanded approval by the FDA to be used alone or combined with rituximab to treat those with relapsed/refractory CLL or SLL, regardless of 17p deletion, who had been administered at least 1 previous therapy. If approved, venetoclax will be available to treat CLL and AML.

Aside from these blood cancers, the drug is also being evaluated in other hematologic malignancies including the following: multiple myeloma, non-Hodgkin lymphoma, and myelodysplastic syndrome.

Known to be a disease that, for the most part, occurs in elderly patients, AML is the most common form of acute leukemia in adults, despite being rare. It is estimated that in 2018 alone, there will be over 19,000 new cases of the aggressive blood cancer and over 10,000 deaths. If left untreated, the disease is known to progress quickly.

Luckily, however, according to Daniel Pollyea, MD, director of the Leukemia Services at the University of Colorado Hospital, “We have an incredible opportunity to develop better treatment options for people with AML.”