The U.S. Food and Drug Administration (FDA) has granted accelerated approval to venetoclax (Venclexta®; Genentech/Roche and Abbvie), in combination with a hypomethylating agent (azacitidine or decitabine), or low-dose cytarabine (LDAC), for the treatment of people with newly-diagnosed Acute Myeloid Leukemia (AML), who are age 75 years or older, or for those ineligible for intensive induction chemotherapy due to coexisting medical conditions.
Acute Myeloid Leukemia is the most common type of aggressive leukemia in adults and has the lowest survival rate for all types of leukemia. In 2018, it is estimated there will be nearly 20,000 new cases of AML diagnosed in the United States. Many AML patients older than age 60 are unable to tolerate intensive induction chemotherapy treatment.
“Today’s approval marks a significant advance for people with acute myeloid leukemia, a highly aggressive and difficult-to-treat blood cancer,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development.
“Many people with acute myeloid leukemia are unable to tolerate standard intensive chemotherapy, and the [venetoclax] combination regimens represent important new options for these patients,” Horning added.
…this approval marks a significant advance for people with acute myeloid leukemia, a highly aggressive and difficult-to-treat blood cancer…
The FDA’s accelerated approval was based on results from two clinical studies the in people newly-diagnosed with AML, including those who were ineligible for intensive induction chemotherapy.
The first study, M14-387, an open-label, single-arm, Phase I/II dose escalation and expansion study designed to evaluate the safety and efficacy of venetoclax in combination with LDAC in newly-diagnosed people with AML who were 60 years or older, or ineligible to receive intensive induction chemotherapy due to coexisting medical conditions, showed a CR rate of 21% (n=13/61) and a CRh rate of 21% (n=13/61) for those who received venetoclax in combination with LDAC.
In the second study, M14-358, an open-label, non-randomized, Phase Ib dose escalation and expansion study evaluating the safety and efficacy of venetoclax in combination with hypomethylating agents, azacitidine or decitabine, in newly-diagnosed people with AML who were 60 years or older, or ineligible to receive intensive induction chemotherapy due to coexisting medical conditions, the rate of Complete Remission (CR) was 37% (n=25/67) and the rate of Complete Remission with partial blood count recovery (CRh) was 24% (n=16/67) for those who received venetoclax + azacitidine. For those who received venetoclax plus decitabine, the rate of CR was 54% (n=7/13) and the rate of CRh was 8% (n=1/13).
The most common serious side effects of these regimens (occurring in at least 5% of patients) were low white blood cell count with fever, pneumonia, bacteria in the blood, inflammation of tissue under the skin, device-related infection, diarrhea, fatigue, bleeding, localized infection, multiple organ dysfunction syndrome and respiratory failure.
The FDA’s Accelerated Approval Program allows conditional approval of a medicine that fills an unmet medical need for a serious condition. This approval of venetoclax is based on surrogate endpoints that are reasonably likely to predict clinical benefit, including CR and CRh. Continued approval for this indication may be contingent upon verification and description of clinical benefit observed in confirmatory trials.
The supplemental New Drug Application (sNDA) was granted Priority Review, a designation given to medicines that the FDA has determined to have the potential to provide significant improvements in the treatment, prevention or diagnosis of a disease. In addition, the FDA previously granted two Breakthrough Therapy Designations for venetoclax in people with previously untreated AML ineligible for intensive chemotherapy, either in combination with a hypomethylating agent or LDAC, based on results from these two studies. With this approval, Venclexta is available in the U.S. for two forms of blood cancer.
Venetoclax is being developed by AbbVie and Genentech. It is jointly commercialized by the companies in the U.S. and commercialized by AbbVie outside of the U.S.
 A Study Evaluating Venetoclax in Combination With Low-Dose Cytarabine in Treatment-Naïve Subjects With Acute Myelogenous Leukemia (AML) – NCT02287233
 Study of ABT-199 (GDC-0199) in Combination With Azacitidine or Decitabine (Chemo Combo) in Subjects With Acute Myelogenous Leukemia (AML) – NCT02203773
Last Editorial Review: November 24, 2018
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