Genentech Announces Submission of Supplemental New Drug Application for Venclexta for People With Previously Untreated Acute Myeloid Leukemia Who Are Ineligible for Intensive Chemotherapy
Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced submission of a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) for Venclexta® (venetoclax), in combination with a hypomethylating agent or in combination with low dose cytarabine (LDAC), for treatment of people with previously untreated acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy. The submission is based on the results of two Phase Ib/II studies that evaluated Venclexta in combination with azacitidine or decitabine (M14-358 study) or LDAC (M14-387 study) in this patient population. Venclexta is being developed by AbbVie and Genentech, a member of the Roche Group. It is jointly commercialized by the companies in the U.S. and commercialized by AbbVie outside of the U.S.
“Nearly 20,000 people will be diagnosed with AML in the U.S. this year, and many of them are not eligible to receive standard intensive chemotherapy,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “AML is an aggressive disease with the lowest survival rate of all leukemias, and we look forward to working closely with the FDA to bring this potential option to patients with this very difficult-to-treat blood cancer as soon as possible.”
Data recently presented from the Phase Ib M14-358 study showed Venclexta in combination with azacitidine or decitabine resulted in a complete remission rate (with or without full recovery of normal blood cell count; CR/CRi) of 73 percent in patients treated with Venclexta at a dose of 400 mg. After more than a year of follow-up, the observed median overall survival (OS) across all Venclexta dose groups in the study was 17.5 months (95 percent CI: 12.3-not reached). The most common Grade 3-4 adverse events (occurring in 10 percent or more patients) were low white blood cell count with fever, low white blood cell count, anemia, low platelet count and decreased potassium levels.
Additionally, results from the Phase Ib/II M14-387 study of Venclexta in combination with LDAC showed a CR/CRi rate of 62 percent in patients treated with Venclexta at a dose of 600 mg. After more than a year of follow-up, the observed median OS was 11.4 months (95 percent CI: 5.7-15.7). The most common Grade 3-4 adverse events (occurring in 10 percent or more patients) were low white blood cell count with fever, decreased potassium levels, pneumonia, disease progression, decreased phosphate levels, high blood pressure and sepsis (blood infection).
The FDA previously granted two breakthrough therapy designations for Venclexta in previously untreated AML ineligible for intensive chemotherapy, either in combination with hypomethylating agents or LDAC, based on results from these two studies. Recently, the FDA approved Venclexta in combination with Rituxan® (rituximab) for the treatment of people with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), with or without 17p deletion, who have received at least one prior therapy. A robust clinical development program is ongoing in several other cancer types.
About the M14-358 study
The M14-358 study (NCT02203773) is an open-label, Phase Ib dose escalation and expansion study evaluating the safety and efficacy of Venclexta in combination with hypomethylating agents, azacitidine or decitabine, in 212 patients who are 60 years or older with previously untreated AML unfit to receive intensive chemotherapy. Study endpoints included CR/CRi, OS and safety.
About the M14-387 study
The M14-387 study (NCT02287233) is an open-label, Phase Ib/II dose escalation and expansion study evaluating the safety and efficacy of Venclexta in combination with LDAC in 94 patients who are 60 years or older with previously untreated AML unfit to receive intensive chemotherapy. Study endpoints included CR/CRi, objective response rate (ORR), OS and safety.
Acute myeloid leukemia (AML) is the most common type of aggressive leukemia in adults, which 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 U.S.
Venclexta is a small molecule designed to selectively bind and inhibit the BCL-2 protein, which plays an important role in a process called apoptosis (programmed cell death). Overexpression of the BCL-2 protein in AML has been associated with resistance to certain therapies. It is believed that blocking BCL-2 may restore the signaling system that tells cells, including cancer cells, to self-destruct. Venclexta is being developed by AbbVie and Genentech, a member of the Roche Group. It is jointly commercialized by the companies in the U.S. and commercialized by AbbVie outside of the U.S.
Together, the companies are committed to further research with Venclexta, which is currently being evaluated in Phase III clinical trials for several types of blood cancers. In the U.S., Venclexta has been granted four Breakthrough Therapy Designations by the FDA: in combination with Rituxan for people with relapsed or refractory CLL; as a monotherapy for people with relapsed or refractory CLL with 17p deletion; in combination with hypomethylating agents (azacitidine or decitabine) for people with untreated AML ineligible for intensive chemotherapy; and in combination with LDAC for people with untreated AML ineligible for intensive chemotherapy.
Venclexta is a prescription medicine used to treat people with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), with or without 17p deletion, who have received at least one prior treatment.
It is not known if Venclexta is safe and effective in children.
Important Safety Information:
Venclexta can cause serious side effects, including:
Tumor lysis syndrome (TLS). TLS is caused by the fast breakdown of cancer cells. TLS can cause kidney failure, the need for dialysis treatment, and may lead to death. A patient’s doctor will do tests for TLS. It is important for patients taking Venclexta to keep their appointments for blood tests. Patients will receive other medicines before starting and during treatment with Venclexta to help reduce the risk of TLS. Patients may also need to receive intravenous (IV) fluids into their vein. Patients taking Venclexta must tell their doctor right away if they have any symptoms of TLS during treatment with Venclexta, including fever, chills, nausea, vomiting, confusion, shortness of breath, seizures, irregular heartbeat, dark or cloudy urine, unusual tiredness, or muscle or joint pain.