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New Data Demonstrate the Continued Clinical Benefit of Fixed-duration, Chemotherapy-free Venclexta-based Treatments in Chronic Lymphocytic Leukemia

– In an updated analysis of the CLL14 study, Venclexta plus Gazyva achieved remissions that were sustained over time in people with previously untreated chronic lymphocytic leukemia –

– At four-year follow-up of the MURANO study, Venclexta plus Rituxan continued to reduce disease progression compared to a standard-of-care therapy in previously treated chronic lymphocytic leukemia –

– Data presented on both studies includes results on minimal residual disease, which is currently emerging as a potential surrogate endpoint –

SOUTH SAN FRANCISCO, Calif.–(BUSINESS WIRE)–Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced updated data from two pivotal Phase III Venclexta® (venetoclax) studies (MURANO and CLL14) that highlight Venclexta combination treatments as chemotherapy-free, fixed-duration options that achieve minimal residual disease (MRD)-negativity, in people with chronic lymphocytic leukemia (CLL). These data and others from the Venclexta clinical development program will be featured in more than 50 abstracts at the 61st American Society of Hematology (ASH) Annual Meeting.

“Venclexta plus anti-CD20 monoclonal antibody-based regimens continue to demonstrate improved long-term outcomes for people with chronic lymphocytic leukemia,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “These results reinforce the sustained clinical benefits observed in patients with this common type of blood cancer, after completing this fixed-duration, chemotherapy-free treatment.”

The pivotal Phase III CLL14 study evaluated the combination of Venclexta plus Gazyva® (obinutuzumab) in people with previously untreated CLL, who had co-existing medical conditions. At a median follow-up of more than three years (39.6 months), when all patients had been off therapy for a minimum of two years, Venclexta plus Gazyva showed high response rates, including MRD-negativity. Specifically:

  • Higher rates of MRD-negativity in peripheral blood (76 percent vs. 35 percent; p<0.001) and bone marrow (57 percent vs. 17 percent; p<0.001) were observed at the end of treatment in people treated with Venclexta plus Gazyva versus Gazyva plus chlorambucil, respectively. MRD-negativity indicates that no cancer can be detected using a specific, highly sensitive test, and was defined as less than one CLL cell in 10,000 white blood cells.
  • MRD-negativity was observed in 42 percent of people treated with Venclexta plus Gazyva who achieved a complete response (CR) in the peripheral blood, and 14 percent of people treated with Gazyva plus chlorambucil (p<0.001). In bone marrow, MRD-negativity was observed in 34 percent of people who achieved a complete response with Venclexta plus Gazyva and 11 percent of people treated with Gazyva plus chlorambucil (p<0.001).
  • At this updated analysis, the fixed-duration, chemotherapy-free combination of Venclexta plus Gazyva reduced the risk of disease worsening or death by 69 percent compared to Gazyva plus chlorambucil (PFS, as assessed by investigator; HR=0.31; 95 percent CI: 0.22-0.44; p<0.0001).
  • The most common Grade 3-4 adverse events (AEs) in people treated with Venclexta plus Gazyva were blood and lymphatic system disorders, and infections.
  • These data were presented on Saturday, December 7, 2019, at 8:45 a.m. ET in an oral session (Abstract #36).

The pivotal Phase III MURANO study evaluated the combination of Venclexta plus Rituxan® (rituximab) in relapsed or refractory (R/R) CLL. Four-year, follow-up data from the study showed sustained OS and PFS benefits with Venclexta plus Rituxan compared to bendamustine plus Rituxan (BR). No new safety events were reported in the study. Specifically:

  • Results showed that Venclexta plus Rituxan significantly reduced the risk of disease progression or death by 81 percent (HR=0.19; 95 percent CI: 0.14, 0.25; p<0.0001) compared to BR, with four-year PFS estimates of 57.3 percent (95 percent CI: 49.4, 65.3) vs. 4.6 percent (95 percent CI: 0.1, 9.2), respectively.
  • Venclexta plus Rituxan also reduced the risk of death by 59 percent (HR=0.41; 95 percent CI: 0.26, 0.65; p<0.0001), compared to BR, with the Venclexta plus Rituxan treatment arm demonstrating greater sustained OS compared to the BR arm, with four-year OS rates of 85.3 percent vs. 66.8 percent, respectively.
  • Venclexta plus Rituxan showed that people who achieved MRD-negativity showed an improvement in PFS at the end of treatment.
  • No new safety signals were identified with the combination in this extended follow-up. Common Grade 3-4 adverse events with Venclexta plus Rituxan compared to BR, respectively, were low white blood cell count (58.8 percent vs. 39.9 percent), anemia (11.3 percent vs. 13.8 percent) and low platelet count (5.7 percent vs. 10.1 percent).
  • Results from the MURANO study were the basis of regulatory approvals for Venclexta plus Rituxan as a treatment option for people with R/R CLL around the world.
  • These data will be presented in an oral session on Sunday, December 8, 2019, at 7:30 a.m. ET (Abstract #355).

Venclexta is being developed by AbbVie and Genentech, a member of the Roche Group. It is jointly commercialized by the companies in the United States and commercialized by AbbVie outside of the United States.

About the CLL14 Study

CLL14 (NCT02242942) is a randomized Phase III study evaluating the combination of fixed-duration Venclexta plus Gazyva compared to Gazyva plus chlorambucil in 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 (IRC), minimal residual disease (MRD) status, overall response (OR), complete response (with or without complete blood count recovery, CR/CRi), overall survival (OS), duration of response (DOR), event-free survival (EFS), time to next CLL treatment (TTNT), and safety. The CLL14 study is being conducted in cooperation with the German CLL Study Group (GCLLSG), headed by Michael Hallek, M.D., University of Cologne.

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 in combination with Rituxan 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 (CLL) 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 (PFS). Secondary endpoints included overall survival (OS), overall response rate (ORR), complete response rate (with or without complete blood count recovery, CR/CRi).

About CLL

Chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia. In the United States, it is estimated that more than 20,000 new cases of CLL will be diagnosed in 2019. Although signs of CLL may disappear for a period of time after initial treatment, the disease is considered incurable and many people will require additional treatment due to the return of cancerous cells.

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 United States and commercialized by AbbVie outside of the United States. 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 United States, Venclexta has been granted five Breakthrough Therapy Designations by the U.S. Food and Drug Administration (FDA): one for previously untreated CLL, two for relapsed or refractory CLL and two for previously untreated acute myeloid leukemia.

Venclexta Indications

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.

    ‒ Venclexta was approved based on response rates. Continued approval for this use may depend on the results of an ongoing study to find out how Venclexta works over a longer period of time.

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 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. 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.
  • 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 counts; low platelet counts; low red blood cell counts; diarrhea; nausea; upper respiratory tract infection; cough; muscle and joint pain; tiredness; and swelling of your 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 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. For more information, patients should ask their doctor or pharmacist.

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.

Gazyva Indications

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:

Patients should 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: These side 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.

Contacts

Media Contact:

Priscilla White (650) 467-6800

Advocacy Contact:

Eydith Comenencia Ortiz (650) 745-5210

Investor Contacts:

Loren Kalm (650) 225-3217

Karl Mahler +41 61 687 85 03

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