Genentech Announces New Data Reinforcing the Long-Term Benefit of Venclexta-Based Combination for People With Relapsed or Refractory Chronic Lymphocytic Leukemia
– Long-term follow-up data from the Phase III MURANO trial showed sustained progression-free survival with fixed-duration Venclexta plus Rituxan –
– MURANO and Phase III CLL14 trials confirm chronic lymphocytic leukemia patients treated with Venclexta-based regimens achieve higher rates of undetectable minimal residual disease*, which may be associated with a lower risk of future disease progression or death –
“These results reinforce the long-term value of fixed-duration, chemotherapy-free Venclexta-based combinations in CLL, potentially offering patients a significant period of time without treatment following initial therapy,” said
Five-year data from the pivotal Phase III MURANO trial continue to show sustained investigator-assessed progression-free survival (PFS) with Venclexta plus Rituxan® (rituximab). Data, presented in an oral session, showed:
- Venclexta plus Rituxan reduced the risk of disease progression or death by 81% (HR=0.19; 95% CI: 0.15, 0.26; p<0.0001) compared to bendamustine plus Rituxan (BR) in people with relapsed or refractory (R/R) CLL.
- At the time of analysis, median overall survival (OS) had not been reached in either arm (HR=0.40; 95% CI: 0.26, 0.62), however, five-year OS was 82.1% in the Venclexta plus Rituxan arm, compared to 62.2% in the BR arm.
- In the Venclexta arm, among the 130 patients who completed two years of treatment without progressive disease, 63.8% (n=83/130) had undetectable MRD (uMRD) levels at the end of treatment. In an analysis of this patient subgroup, uMRD was associated with improved progression-free survival. Undetectable MRD, sometimes referred to as MRD-negativity, means that no cancer cells could be detected using a specific and highly sensitive test, and is defined as less than one cancer cell in 10,000 leukocytes.
- No new safety events were reported in the study.
Data from the Phase III CLL14 study contributes to growing evidence regarding the potential of MRD measurements to predict future outcomes for certain people with previously untreated CLL who were treated with fixed-duration Venclexta plus Gazyva® (obinutuzumab):
- Patients with uMRD and a partial response (PR) had longer PFS than patients with detectable MRD and a complete response (CR).
- In collaboration with Adaptive Biotechnologies, clonal growth rate, a measure for how quickly cancer cells grow, was analyzed using the next-generation sequencing Adaptive clonoSEQ® Assay and insights were used to better understand the potential role of MRD in predicting outcomes. In this analysis, after treatment with fixed-duration Venclexta plus Gazyva, the estimated clonal growth rate was slower and lower, suggesting more effective MRD eradication in these patients compared to those treated with Gazyva plus chlorambucil. Early data suggest a correlation between MRD responses and PFS, which will be further evaluated by the study authors.
Exploring novel endpoints, such as MRD, is an important area of development for
Venclexta is being developed by AbbVie and
*Minimal residual disease (MRD) is a measure of the number of remaining cancer cells. Undetectable MRD (uMRD), sometimes referred to as MRD-negativity, means that no cancer cells could be detected using a specific and highly sensitive test, and is defined as less than one cancer cell in 10,000 leukocytes.
About the MURANO Study
MURANO [NCT02005471] is a Phase III open-label, international, multicenter, randomized study evaluating the efficacy and safety of fixed-duration Venclexta® (venetoclax) in combination with Rituxan® (rituximab) compared to bendamustine in combination with Rituxan (BR). All treatments were of fixed duration. Following a five-week dose ramp-up schedule for Venclexta, patients on the Venclexta plus Rituxan arm received six cycles of Venclexta plus Rituxan followed by Venclexta monotherapy for up to two years total. Patients on the BR arm received six cycles of BR. The study included 389 patients with chronic lymphocytic leukemia, with or without 17p deletion, who had been previously treated with at least one line of therapy. Patients were randomly assigned in a 1:1 ratio to receive either Venclexta plus Rituxan or BR. The primary endpoint of the study was progression-free survival. Secondary endpoints included overall survival, overall response rate and complete response rate (with or without complete blood count recovery).
About the CLL14 Study
CLL14 [NCT02242942] is a randomized Phase III study evaluating the combination of fixed-duration Venclexta® (venetoclax) plus Gazyva® (obinutuzumab) compared to Gazyva plus chlorambucil in adult patients with previously untreated chronic lymphocytic leukemia (CLL) and co-existing medical conditions. 432 patients with previously untreated CLL were randomly assigned to receive either a 12-month duration of Venclexta alongside six-month duration of Gazyva (Arm A) or six-month duration of Gazyva alongside 12-month duration of chlorambucil (Arm B). Arm A started with an initial dosing of Gazyva followed by a five-week Venclexta dose ramp-up to help reduce the risk of tumor burden. The primary endpoint of the study is investigator-assessed progression-free survival (PFS). Secondary endpoints include PFS assessed by independent review committee, minimal residual disease (MRD) status, overall response rate, complete response rate (with or without complete blood count recovery), overall survival, duration of response, event-free survival, time to next CLL treatment, and safety. MRD-negativity, or undetectable MRD, means no cancer can be detected using a specific and highly sensitive test, and was defined as less than one cancer cell in 10,000 leukocytes. The CLL14 study is being conducted in cooperation with the
Chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia. In
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
Venclexta is a prescription medicine used:
- to treat adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
- 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
What is the most important information patients should know about Venclexta?
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 into 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. When restarting Venclexta after stopping for 1 week or longer, the patient’s doctor may again check for the risk of TLS and change the patient’s dose.
What patients should not take Venclexta?
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 TLS.
- Patients should 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 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. Patients 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 are instructed to not breastfeed during treatment with Venclexta and for 1 week after the last dose.
What to avoid while taking Venclexta:
Patients should not drink grapefruit juice or eat grapefruit,
What are the possible side effects of Venclexta?
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 and may pause dosing.
- Infections. Death and serious infections such as pneumonia and blood infection (sepsis) have happened during treatment with Venclexta. The patient’s doctor will closely monitor and treat the patient right away if they have a fever or any signs of infection 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 obinutuzumab or rituximab or alone in people with CLL or SLL include low white blood cell count;low platelet count; low red blood cell count;diarrhea; nausea; upper respiratory tract infection; cough; muscle and joint pain; tiredness; and swellingof arms, legs, hands, and feet.
The most common side effects of Venclexta in combination with azacitidine or decitabine or low-dose cytarabine in people with AML include nausea; diarrhea; low platelet count; constipation; low white blood cell count; fever with low white blood cell count; tiredness; vomiting; swelling of arms, legs, hands, or feet; fever; infection in lungs; shortness of breath; bleeding; low red blood cell count; rash; stomach (abdominal) pain; infection in your blood; muscle and joint pain; dizziness; cough; sore throat; and low blood pressure.
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 call their doctor for medical advice about side effects.
Report side effects to the FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch. Report side effects to
Rituxan® (rituximab) is a prescription medicine used to treat adults with:
- Non-Hodgkin’s lymphoma (NHL): alone or with other chemotherapy medicines
- Chronic lymphocytic leukemia (CLL): with the chemotherapy medicines fludarabine and cyclophosphamide.
Important Safety Information:
Rituxancan cause serious side effects that can lead to death, including:
Infusion-Related Reactions: Infusion-related reactions are very common side effects of Rituxan treatment. Serious infusion-related 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-related 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 rash
- Swelling of the lips, tongue, throat, or face
- Sudden cough
- Shortness of breath, difficulty breathing, or wheezing
- Dizziness or feel faint
- Palpitations (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 mouth
- Peeling skin
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:
- Dizziness or loss of balance
- Difficulty walking or talking
- Decreased strength or weakness on one side of the body
- Vision 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 B19
- Varicella 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 treatment
- Abnormal 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:
- Lack 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:
- Cold symptoms, such as runny nose or sore throat that do not go away
- Flu symptoms, such as cough, tiredness, and body aches
- Earache or headache
- Pain during urination
- Cold sores in the mouth or throat
- Cuts, 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
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 http://www.fda.gov/medwatch. Report side effects to
Gazyva® (obinutuzumab) is a prescription medicine used:
- With the chemotherapy drug, chlorambucil, to treat chronic lymphocytic leukemia (CLL) in adults who have not had previous CLL treatment.
- With the chemotherapy drug, bendamustine, followed by Gazyva alone for follicular lymphoma (FL) in adults who did not respond to a rituximab-containing regimen, or whose FL returned after such treatment.
- With chemotherapy, followed by Gazyva alone in those who responded, to treat stage II bulky, III, or IV FL in adults who have not had previous FL treatment.
Important Safety Information
The most important safety information patients should know about Gazyva
Patients must tell their doctor right away about any side effect they experience. Gazyva can cause side effects that can become serious or life threatening, including:
- Hepatitis B Virus (HBV): Hepatitis B can cause liver failure and death. If the patient has a history of hepatitis B infection, Gazyva could cause it to return. Patients should not receive Gazyva if they have active hepatitis B liver disease. The patient’s doctor or healthcare team will need to screen them for hepatitis B before, and monitor the patient for hepatitis during and after, their treatment with Gazyva. Sometimes this will require treatment for hepatitis B. Symptoms of hepatitis include: worsening of fatigue and yellow discoloration of skin or eyes.
- Progressive Multifocal Leukoencephalopathy (PML): PML is a rare and serious brain infection caused by a virus. PML can be fatal. The patient’s weakened immune system could put them at risk. The patient’s doctor will watch for symptoms. Symptoms of PML include: confusion, difficulty talking or walking, dizziness or loss of balance, and vision problems.
Who should not receive Gazyva:
Patientsshould NOT receive Gazyva if they have had an allergic reaction (e.g., anaphylaxis or serum sickness) to Gazyva.Patients must tell their healthcare provider if they have had an allergic reaction to obinutuzumab or any other ingredients in Gazyva in the past.
Additional possible serious side effects of Gazyva:
Patients must tell their doctor right away about any side effect they experience. Gazyva can cause side effects that may become severe or life threatening, including:
- Infusion Reactions: Theseside effects may occur during or within 24 hours of any Gazyva infusion. Some infusion reactions can be serious, including, but not limited to, severe allergic reactions (anaphylaxis), acute life-threatening breathing problems, or other life-threatening infusion reactions. If the patient has a reaction, the infusion is either slowed or stopped until their symptoms are resolved. Most patients are able to complete infusions and receive medication again. However, if the infusion reaction is life threatening, the infusion of Gazyva will be permanently stopped. The patient’s healthcare team will take steps to help lessen any side effects the patient may have to the infusion process. The patient may be given medicines to take before each Gazyva treatment. Symptoms of infusion reactions may include: fast heartbeat, tiredness, dizziness, headache, redness of the face, nausea, chills, fever, vomiting, diarrhea, rash, high blood pressure, low blood pressure, difficulty breathing, and chest discomfort.
- Hypersensitivity Reactions Including Serum Sickness: Some patients receiving Gazyva may have severe or life-threatening allergic reactions. This reaction may be severe, may happen during or after an infusion, and may affect many areas of the body. If an allergic reaction occurs, the patient’s doctor will stop the infusion and permanently discontinue Gazyva.
- Tumor Lysis Syndrome (TLS): Tumor lysis syndrome, including fatal cases, has been reported in patients receiving Gazyva. Gazyva works to break down cancer cells quickly. As cancer cells break apart, their contents are released into the blood. These contents may cause damage to organs and the heart, and may lead to kidney failure requiring the need for dialysis treatment. The patient’s doctor may prescribe medication to help prevent TLS. The patient’s doctor will also conduct regular blood tests to check for TLS. Symptoms of TLS may include nausea, vomiting, diarrhea, and tiredness.
- Infections: While the patient is taking Gazyva, they may develop infections. Some of these infections may be fatal and severe, so the patient should be sure to talk to their doctor if they think they have an infection. Patients administered Gazyva in combination with chemotherapy, followed by Gazyva alone are at a high risk of infections during and after treatment. Patients with a history of recurring or chronic infections may be at an increased risk of infection. Patients with an active infection should not be treated with Gazyva. Patients taking Gazyva plus bendamustine may be at higher risk for fatal or severe infections compared to patients taking Gazyva plus CHOP or CVP.
- Low White Blood Cell Count: When the patient has an abnormally low count of infection-fighting white blood cells, it is called neutropenia. While the patient is taking Gazyva, their doctor will do blood work to check their white blood cell count. Severe and life-threatening neutropenia can develop during or after treatment with Gazyva. Some cases of neutropenia can last for more than one month. If the patient’s white blood cell count is low, their doctor may prescribe medication to help prevent infections.
- Low Platelet Count: Platelets help stop bleeding or blood loss. Gazyva may reduce the number of platelets the patient has in their blood; having low platelet count is called thrombocytopenia. This may affect the clotting process. While the patient is taking Gazyva, their doctor will do blood work to check their platelet count. Severe and life-threatening thrombocytopenia can develop during treatment with Gazyva. Fatal bleeding events have occurred in patients treated with Gazyva. If the patient’s platelet count gets too low, their treatment may be delayed or reduced.
The most common side effects of Gazyva in CLL were infusion reactions, low white blood cell counts, low platelet counts, low red blood cell counts, fever, cough, nausea, and diarrhea.
The safety of Gazyva was evaluated based on 392 patients with relapsed or refractory NHL, including FL (81 percent), small lymphocytic lymphoma (SLL) and marginal zone lymphoma (MZL) (a disease for which Gazyva is not indicated), who did not respond to or progressed within 6 months of treatment with rituximab product or a rituximab product-containing regimen. In patients with follicular lymphoma, the profile of side effects that were seen were consistent with the overall population who had NHL. The most common side effects of Gazyva were infusion reactions, low white blood cell counts, nausea, fatigue, cough, diarrhea, constipation, fever, low platelet counts, vomiting, upper respiratory tract infection, decreased appetite, joint or muscle pain, sinusitis, low red blood cell counts, general weakness, and urinary tract infection.
A randomized, open-label multicenter trial (GALLIUM) evaluated the safety of Gazyva as compared to rituximab product in 1,385 patients with previously untreated follicular lymphoma (86 percent) or marginal zone lymphoma (14 percent). The most common side effects of Gazyva were infusion reactions, low white blood cell count, upper respiratory tract infection, cough, constipation and diarrhea.
Before receiving Gazyva, patients should talk to their doctor about:
- Immunizations: Before receiving Gazyva therapy, the patient should tell their healthcare provider if they have recently received or are scheduled to receive a vaccine. Patients who are treated with Gazyva should not receive live vaccines.
- Pregnancy: The patient should tell their doctor if they are pregnant, think that they might be pregnant, plan to become pregnant, or are breastfeeding. Gazyva may harm their unborn baby. The patient should speak to their doctor about using Gazyva while they are pregnant. The patient should talk to their doctor or their child’s doctor about the safety and timing of live virus vaccinations to their infant if they received Gazyva during pregnancy. It is not known if Gazyva may pass into the patient’s breast milk. The patient should speak to their doctor about using Gazyva if they are breastfeeding.
Patients should tell their doctor about any side effects.
These are not all of the possible side effects of Gazyva. For more information, patients should ask their doctor or pharmacist.
Gazyva is available by prescription only.
Report side effects to the FDA at (800) FDA-1088, or http://www.fda.gov/medwatch. Report side effects to
Please visit http://www.Gazyva.com for the Gazyva full Prescribing Information, including BOXED WARNINGS, for additional Important Safety Information.
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