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Genentech Announces Submission of Supplemental New Drug Application for Venclexta for People With Previously Untreated Acute Myeloid Leukemia Who Are Ineligible for Intensive Chemotherapy

July 12, 2018

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Jul 12, 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.

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 U.S.

About Venclexta

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 Indication

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 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 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.

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 or liver problems. Have problems with their body salts or electrolytes, such as potassium, phosphorus, or calcium. Have a history of high uric acid levels in their blood or gout. Are scheduled to receive a vaccine. Patients should not receive a “live vaccine” before, during, or after treatment with Venclexta until their doctor tells them it is okay. If a patient is not sure about the type of immunization or vaccine, they 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 a patient is able to become pregnant, the doctor should do a pregnancy test before they start treatment with Venclexta, and they should use effective birth control during treatment and for 30 days after the last dose of Venclexta. Are breastfeeding or plan to breastfeed. It is not known if Venclexta passes into breast milk. Patients should not breastfeed during treatment with Venclexta.

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:

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

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 . Patients and caregivers may also report side effects to Genentech at (888) 835-2555.

Please visit for the Venclexta full Prescribing Information, including Patient Information, for additional Important Safety Information.

Rituxan Indications

Rituxan ® (rituximab) injection, for intravenous use, is indicated for the treatment of:

Low-grade or follicular CD20-positive non-Hodgkin’s lymphoma as a single-agent therapy in patients whose disease recurred or did not respond to initial treatment Follicular CD20-positive non-Hodgkin’s lymphoma as an initial treatment with chemotherapy, and in patients whose initial treatment was successful, as a single-agent follow-up therapy Low-grade CD20-positive non-Hodgkin’s lymphoma as a single-agent follow-up therapy for patients who did not progress on initial treatment with CVP chemotherapy CD20-positive diffuse large B-cell non-Hodgkin’s lymphoma as an initial treatment in combination with CHOP chemotherapy CD20-positive chronic lymphocytic leukemia in combination with FC chemotherapy as an initial treatment or as a treatment after disease has recurred

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:

Infusion Reactions: Infusion reactions are very common side effects of Rituxan treatment. Serious infusion reactions can happen during the patient’s infusion or within 24 hours after the patient’s infusion of Rituxan. The patient’s doctor should give the patient medicines before infusion of Rituxan to decrease the chance of having a severe infusion reaction. Patients must tell their doctor or get medical help right away about any of these symptoms during or after an infusion of Rituxan: Hives (red itchy welts) or rashItchingSwelling of the lips, tongue, throat, or faceSudden coughShortness of breath, difficulty breathing, or wheezingWeaknessDizziness or feel faintPalpitations (feel like the heart is racing or fluttering)Chest pain Severe Skin and Mouth Reactions: Patients must tell their doctor or get medical help right away about any of these symptoms at any time during treatment with Rituxan: Painful sores or ulcers on the skin, lips, or in the mouthBlistersPeeling skinRashPustules Hepatitis B Virus (HBV) Reactivation: Before receiving Rituxan treatment, the patient’s doctor will do blood tests to check for HBV infection. If the patient has had hepatitis B or is a carrier of hepatitis B virus, receiving Rituxan could cause the virus to become an active infection again. Hepatitis B reactivation may cause serious liver problems, including liver failure, and death. The patient’s doctor will monitor for hepatitis B infection during and for several months after the patient stops receiving 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. Progressive Multifocal Leukoencephalopathy (PML): PML is a rare, serious brain infection caused by a virus that can happen in people who receive Rituxan. People with weakened immune systems can get PML. PML can result in death or severe disability. There is no known treatment, prevention, or cure for PML. Patients must tell their doctor right away about new or worsening symptoms or if anyone close to the patient notices these symptoms: ConfusionDizziness or loss of balanceDifficulty walking or talkingDecreased strength or weakness on one side of the bodyVision problems, such as blurred vision or loss of vision

What should patients tell their doctor before receiving Rituxan?

Before receiving Rituxan, patients should tell their doctor if they:

Have had a severe reaction to Rituxan or a rituximab product Have a history of heart problems, irregular heartbeat, or chest pain Have lung or kidney problems Have had an infection, currently have an infection, or have a weakened immune system Have or have had any severe infections including: Hepatitis B virus (HBV)Hepatitis C virus (HCV)Cytomegalovirus (CMV)Herpes simplex virus (HSV)Parvovirus B19Varicella zoster virus (chickenpox or shingles)West Nile Virus Have had a recent vaccination or are scheduled to receive vaccinations. Patients should not receive certain vaccines before or during treatment with Rituxan Have any other medical conditions Are pregnant or plan to become pregnant. Patients must talk to their doctor about the risks to the patient’s unborn baby if receiving Rituxan during pregnancy. Females who are able to become pregnant should use effective birth control (contraception) during treatment with Rituxan and for 12 months after the last dose of Rituxan. Patients should talk to their doctor about effective birth control. Patients should tell their doctor right away if they become pregnant or think that they are pregnant during treatment with Rituxan Are breastfeeding or plan to breastfeed. It is not known if Rituxan passes into the breast milk. Do not breastfeed during treatment and for at least 6 months after the last dose of Rituxan Are taking any medications, including prescription and over-the-counter medicines, vitamins, and herbal supplements

What are the possible side effects of Rituxan?

Rituxan can cause serious side effects, including:

Tumor Lysis Syndrome (TLS): TLS is caused by the fast breakdown of cancer cells. TLS can cause the patient to have: Kidney failure and the need for dialysis treatmentAbnormal heart rhythm TLS can happen within 12 to 24 hours after an infusion of Rituxan. The patient’s doctor may do blood tests to check for TLS. The patient’s doctor may give medicine to help prevent TLS. Patients must tell their doctor right away if they have any of the following signs or symptoms of TLS: NauseaVomitingDiarrheaLack of energy Serious Infections: Serious infections can happen during and after treatment with Rituxan, and can lead to death. Rituxan can increase the patient’s risk of getting infections and can lower the ability of the patient’s immune system to fight infections. Types of serious infections that can happen with Rituxan include bacterial, fungal, and viral infections. After receiving Rituxan, some people have developed low levels of certain antibodies in their blood for a long period of time (longer than 11 months). Some of these patients with low antibody levels developed infections. People with serious infections should not receive Rituxan. Patients must tell their doctor right away if they have any symptoms of infection: FeverCold symptoms, such as runny nose or sore throat that do not go awayFlu symptoms, such as cough, tiredness, and body achesEarache or headachePain during urinationCold sores in the mouth or throatCuts, scrapes, or incisions that are red, warm, swollen, or painful Heart Problems: Rituxan may cause chest pain, irregular heartbeats, and heart attack. The patient’s doctor may monitor the patient’s heart during and after treatment with Rituxan if they have symptoms of heart problems or have a history of heart problems. Patients must tell their doctor right away if they have chest pain or irregular heartbeats during treatment with Rituxan. Kidney Problems: especially if the patient is receiving Rituxan for NHL. Rituxan can cause severe kidney problems that lead to death. The patient’s doctor should do blood tests to check how well their kidneys are working. Stomach and Serious Bowel Problems That Can Sometimes Lead to Death: Bowel problems, including blockage or tears in the bowel can happen if the patient receives Rituxan with chemotherapy medicines. Patients must tell their doctor right away if they have any stomach-area (abdomen) pain or repeated vomiting during treatment with Rituxan.

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?

Infusion-related reactions Infections (may include fever, chills) Body aches Tiredness Nausea

Other side effects include:

Aching joints during or within hours of receiving an infusion More frequent upper respiratory tract infections

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 . 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.

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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CONTACT: Genentech

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SOURCE: Genentech

Copyright Business Wire 2018.

PUB: 07/12/2018 01:01 AM/DISC: 07/12/2018 01:01 AM

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