Genentech Announces FDA Grants Venclexta Accelerated Approval for People With Newly-Diagnosed Acute Myeloid Leukemia or Those Who Are Ineligible for Intensive Induction Chemotherapy

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)-- Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today that the U.S. Food and Drug Administration (FDA) has granted accelerated approval to Venclexta^® (venetoclax), 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. AML is the most common type of aggressive leukemia in adults and has the lowest survival rate for all types of leukemia.

“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 Venclexta combination regimens represent important new options for these patients.”

This accelerated approval was based on results from the M14-358 study and the M14-387 study in people newly-diagnosed with AML including those who were ineligible for intensive induction chemotherapy. In M14-358, the rate of complete remission (CR) was 37 percent (n=25/67) and the rate of complete remission with partial blood count recovery (CRh) was 24 percent (n=16/67) for those who received Venclexta plus azacitidine. For those who received Venclexta plus decitabine, the rate of CR was 54 percent (n=7/13) and the rate of CRh was 8 percent (n=1/13). M14-387 showed a CR rate of 21 percent (n=13/61) and a CRh rate of 21 percent (n=13/61) for those who received Venclexta in combination with LDAC.

The most common serious side effects of these regimens (occurring in at least 5 percent 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 Venclexta 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 Venclexta 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.

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.

About the M14-358 study

The M14-358 study (NCT02203773) is an open-label, non-randomized, Phase Ib dose escalation and expansion study evaluating the safety and efficacy of Venclexta 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. Study endpoints included complete remission rates, overall survival and safety.

• In M14-358, the rate of CR was 37 percent and the rate of CRh was 24 percent for those who received Venclexta plus azacitidine. The median follow-up for this group was 7.9 months (0.4-36 months). At the time of analysis, for patients who achieved a CR, the median observed time in remission was 5.5 months (0.4-30 months).
• For those who received Venclexta plus decitabine, the rate of CR was 54 percent and the rate of CRh was 8 percent. The median follow-up for this group was 11 months (0.7-21 months). At the time of analysis, for patients who achieved a CR, the median observed time in remission was 4.7 months (1.0-18 months).
• The observed time in remission for these regimens was defined as the time from the start of CR to the time of the data cut-off date or relapse from CR.
• The most common adverse reactions with Venclexta plus azacitidine were nausea, diarrhea, constipation, low white blood cell count with or without fever, low platelet count, bleeding, swelling in the arms, legs, hands and feet, vomiting, fatigue, rash and low red blood cell count.
• The most common adverse reactions with Venclexta plus decitabine were low white blood cell count with or without fever, constipation, fatigue, low platelet count, stomach (abdominal) pain, dizziness, bleeding, nausea, pneumonia, infection in the blood, cough, diarrhea, low blood pressure, pain in muscles or back, sore throat, swelling in the arms, legs, hands and feet, fever and rash.

About the M14-387 study

The M14-387 study (NCT02287233) is an open-label, single-arm, Phase I/II dose escalation and expansion study evaluating the safety and efficacy of Venclexta 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. Study endpoints included complete remission rates, overall survival and safety.

• The study showed the rate of CR and CRh was 21 percent for those who received Venclexta plus LDAC. The median follow-up for this group was 6.5 months (0.3-34 months). At the time of analysis, for patients who achieved a CR, the median observed time in remission was 6.0 months (0.03-25 months). The observed time in remission for this regimen was defined as the time from the start of CR to the time of the data cut-off date or relapse from CR.
• The most common adverse reactions with Venclexta in combination with LDAC were nausea, low platelet count, bleeding, low white blood cell count with or without fever, diarrhea, fatigue, constipation and difficulty breathing.

About AML

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 United States. Many AML patients older than age 60 are unable to tolerate intensive induction chemotherapy treatment.

About Genentech Access Solutions

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About Venclexta

Venclexta is a first-in-class targeted medicine designed to selectively bind and inhibit the B-cell lymphoma-2 (BCL-2) protein. In some blood cancers and other tumors, BCL-2 builds up and prevents cancer cells from dying or self-destructing, a process called apoptosis. Venclexta blocks the BCL-2 protein and works to restore the process of apoptosis.

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 research with Venclexta, which is currently being studied in clinical trials across several types of blood and other 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 chronic lymphocytic leukemia (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 acute myeloid leukemia (AML) ineligible for intensive chemotherapy; and in combination with low-dose cytarabine for people with untreated AML ineligible for intensive chemotherapy.

Venclexta Indications

Venclexta is a prescription medicine used:

• To treat adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), with or without 17p deletion, who have received at least 1 prior treatment.
• In combination with azacitidine, or decitabine, or low-dose cytarabine to treat adults with newly-diagnosed acute myeloid leukemia (AML) who:
  ‒ Are 75 years of age or older, or
  ‒ Have other medical conditions that prevent the use of standard chemotherapy.

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. The patient’s doctor will do tests to check their risk of getting TLS before they start taking Venclexta. The patient will receive other medicines before starting and during treatment with Venclexta to help reduce the risk of TLS. The patient may also need to receive intravenous (IV) fluids through their vein.

The patient’s doctor will do blood tests to check for TLS when the patient first starts treatment and during treatment with Venclexta. It is important for patients to keep appointments for blood tests. Patients should 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 during treatment with Venclexta to help 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 the first dose, on the day of the first dose of Venclexta, and each time a dose is increased.

The patient’s doctor may delay, decrease the dose, or stop treatment with Venclexta if the patient has side effects.

Certain medicines must not be taken when the patient first starts taking Venclexta and while the dose is being slowly increased because of the risk of increased tumor lysis syndrome.

• Patients must tell their doctor about all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Venclexta and other medicines may affect each other, causing serious side effects.
• Patients must not start new medicines during treatment with Venclexta without first talking with their doctor.

Before taking Venclexta, patients must tell their doctor about all of their medical conditions, including if they:

• Have kidney problems.
• Have problems with body salts or electrolytes, such as potassium, phosphorus, or calcium.
• Have a history of high uric acid levels in the blood or gout.
• Are scheduled to receive a vaccine. The patient should not receive a “live vaccine” before, during, or after treatment with Venclexta, until the patient’s doctor tells them it is okay. If the patient is not sure about the type of immunization or vaccine, the patient should ask their doctor. These vaccines may not be safe or may not work as well during treatment with Venclexta.
• Are pregnant or plan to become pregnant. Venclexta may harm an unborn baby. If the patient is able to become pregnant, the patient’s doctor should do a pregnancy test before the patient starts treatment with Venclexta, and the patient should use effective birth control during treatment and for at least 30 days after the last dose of Venclexta. If the patient becomes pregnant or thinks they are pregnant, the patient should tell their doctor right away.
• Are breastfeeding or plan to breastfeed. It is not known if Venclexta passes into the patient’s breast milk. Patients should not breastfeed during treatment with Venclexta.

What to avoid while taking Venclexta:

Patients should not drink grapefruit juice, 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:

• Low white blood cell counts (neutropenia). Low white blood cell counts are common with Venclexta, but can also be severe. The patient’s doctor will do blood tests to check their blood counts during treatment with Venclexta. Patients should tell their doctor right away if they have a fever or any signs of an infection during treatment with Venclexta.

The most common side effects of Venclexta when used in combination with rituximab in people with CLL include low white blood cell counts; diarrhea; upper respiratory tract infection; cough; tiredness; and nausea.

The most common side effects of Venclexta when used alone in people with CLL/SLL include low white blood cell counts; diarrhea; nausea; upper respiratory tract infection; low red blood cell counts; tiredness; low platelet counts; muscle and joint pain; swelling of arms, legs, hands, and feet; and cough.

The most common side effects of Venclexta in combination with azacitidine, or decitabine, or low-dose cytarabine in people with AML include low white blood cell counts; nausea; diarrhea; low platelet counts; constipation; fever with low white blood cell counts; low red blood cell counts; infection in blood; rash; dizziness; low blood pressure; fever; swelling of arms, legs, hands, and feet; vomiting; tiredness; shortness of breath; bleeding; infection in lung; stomach (abdominal) pain; pain in muscles or back; cough; and sore throat.

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 should tell their doctor about any side effect that bothers them or that does not go away.

Report side effects to the FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch. Report side effects to Genentech at 1-888-835-2555.

Please visit http://www.Venclexta.com for the Venclexta full Prescribing Information, including Patient Information, for additional Important Safety Information.

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.

About Genentech

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.

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