Wednesday, Jul 11, 2018
Venclexta represents a potential new way of treating AML, the most common type of aggressive leukemia in adults
South San Francisco, CA -- July 11, 2018 --
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.
Patients should drink plenty of water when taking Venclexta
reduce the risk of getting TLS.
Patients should drink 6 to 8 glasses (about 56 ounces total) of water each day, starting 2 days before their first dose, on the day of their first dose of Venclexta, and each time the dose is increased.
Certain medicines must not be taken when patients first start taking Venclexta and while their dose is being slowly increased because of the risk of increased tumor lysis syndrome.
Before taking Venclexta, patients must tell their doctor about all of their medical conditions, including if they:
Patients should not drink grapefruit juice or eat grapefruit, Seville oranges (often used in marmalades), or starfruit while they are taking Venclexta. These products may increase the amount of Venclexta in the patient’s blood.
Venclexta can cause serious side effects, including:
The most common side effects of Venclexta when used in combination with rituximab include low white blood cell count, diarrhea, upper respiratory tract infection, cough, tiredness, and nausea.
The most common side effects of Venclexta when used alone include low white blood cell count, diarrhea, nausea, upper respiratory tract infection, low red blood cell count, tiredness, low platelet count, muscle and joint pain, swelling of the arms, legs, hands, and feet, and cough.
Venclexta may cause fertility problems in males. This may affect the ability to father a child. Patients should talk to their doctor if they have concerns about fertility.
These are not all the possible side effects of Venclexta. Patients must tell their doctor if they have any side effect that bothers them or that does not go away.
Report side effects to the FDA at (800) FDA-1088 or http://www.fda.gov/medwatch. Patients and caregivers may also report side effects to Genentech at (888) 835-2555.
Please visit http://www.Venclexta.com for the Venclexta full Prescribing Information, including Patient Information, for additional Important Safety Information.
Rituxan® (rituximab) injection, for intravenous use, is indicated for the treatment of:
It is not known if Rituxan is safe and effective in children.
Important Safety Information:
Rituxan can cause serious side effects that can lead to death, including:
Patients must tell their doctor or get medical help right away about any of these symptoms during or after an infusion of Rituxan:
Patients must tell their doctor right away about worsening tiredness, or yellowing of the skin or white part of the eyes during treatment with Rituxan.
Patients must tell their doctor right away about new or worsening symptoms or if anyone close to the patient notices these symptoms:
What should patients tell their doctor before receiving Rituxan?
Before receiving Rituxan, patients should tell their doctor if they:
What are the possible side effects of Rituxan?
Rituxan can cause serious side effects, including:
The patient’s doctor will stop treatment with Rituxan if they have severe, serious, or life-threatening side effects.
What are the most common side effects during treatment with Rituxan?
Other side effects include:
These are not all of the possible side effects with Rituxan.
Please see the Rituxan full Prescribing Information, including the Medication Guide, for additional Important Safety Information at http://www.Rituxan.com.
Report side effects to the FDA at (800) FDA-1088 or http://www.fda.gov/medwatch. Report side effects to Genentech at (888) 835-2555.
About Genentech in Hematology
For more than 20 years, Genentech has been developing medicines with the goal to redefine treatment in hematology. Today, we’re investing more than ever in our effort to bring innovative treatment options to people with diseases of the blood. For more information visit http://www.gene.com/hematology.
Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.