Tuesday, Jun 4, 2019
Chicago -- June 4, 2019 --
Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced results from the pivotal Phase III CLL14 study in previously untreated chronic lymphocytic leukemia (CLL) showing that Venclexta® (venetoclax) plus Gazyva® (obinutuzumab) met its primary endpoint of investigator-assessed progression-free survival (PFS). The 12-month, fixed-duration, chemotherapy-free combination reduced the risk of disease worsening or death by 65 percent compared to Gazyva plus chlorambucil (PFS, as assessed by investigator; HR=0.35; 95 percent CI 0.23-0.53; p<0.001), when given to people with previously untreated CLL who have co-existing medical conditions. The results were presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting and simultaneously published in the New England Journal of Medicine (NEJM).
At two years, one year after stopping treatment, nearly nine out of ten patients (88.2 percent) in the Venclexta plus Gazyva arm remained progression-free, compared to 64.1 percent in the Gazyva plus chlorambucil arm. Safety for Venclexta plus Gazyva appeared consistent with the known safety profiles of the individual medicines. Common Grade 3-4 adverse events with Venclexta plus Gazyva compared to Gazyva plus chlorambucil, respectively, were low white blood cell count (52.8 percent vs. 48.1 percent) and infections (17.5 percent vs. 15.0 percent).
“The results of our Phase III CLL14 trial, reported today at ASCO and in the New England Journal of Medicine, represent a major advance in improving outcomes in chronic lymphocytic leukemia,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “We are pleased this fixed-duration, chemotherapy-free regimen of Venclexta plus Gazyva was approved by the FDA and look forward to providing an important treatment option to even more adults with the most common form of adult leukemia.”
The treatment benefit demonstrated with the Venclexta plus Gazyva combination compared to Gazyva plus chlorambucil was consistent across secondary endpoints, including:
These data were presented at the 2019 ASCO Annual Meeting on Tuesday, June 4, 2019, at 10:09-10:21 CST (Abstract #7502), and simultaneously published in NEJM.
The U.S. Food and Drug Administration (FDA) approved the combination on May 15, 2019, under the FDA’s Real-Time Oncology Review and Assessment Aid pilot programs, for the treatment of people with previously untreated CLL or small lymphocytic lymphoma. This is the second regimen of Genentech medicines approved under the RTOR pilot program, which is exploring a more efficient review process to ensure safe and effective treatments are available to patients as early as possible. Additional submissions of the CLL14 data to health authorities around the world are ongoing.
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. Co-existing medical conditions included reduced kidney function or co-morbidities assessed by a standard scale (Cumulative Illness Rating Scale). 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 lysis syndrome. 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 rate (ORR), complete response (with or without complete blood count recovery), overall survival, duration of response, event-free survival, time to next CLL treatment, and safety. The CLL14 study is being conducted in cooperation with the German CLL Study Group, headed by Michael Hallek, M.D., University of Cologne.
After a median follow-up of 28 months, results showed:
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.
In CLL, the cancer primarily occurs in the blood and bone marrow. Small lymphocytic lymphoma (SLL) is similar to CLL, but primarily occurs in the lymph nodes.
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.
Gazyva is an engineered monoclonal antibody designed to attach to CD20, a protein found only on certain types of B-cells. Gazyva is designed to attack and destroy targeted B-cells both directly and together with the body's immune system. Gazyva was discovered by Roche Innovation Center Zurich, formerly Roche Glycart AG, a wholly owned, independent research unit of Roche. In the United States, Gazyva is part of a collaboration between Genentech and Biogen.
Additional combination studies investigating Gazyva with other approved or investigational medicines, including cancer immunotherapies and small molecule inhibitors, are underway across a range of blood cancers.
Venclexta is a prescription medicine used:
‒ 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.
Before taking Venclexta, patients must tell their doctor about all of their medical conditions, including if they:
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:
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. 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.
Gazyva® (obinutuzumab) is a prescription medicine used:
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:
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:
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:
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 Genentech at (888) 835-2555.
Please visit http://www.Gazyva.com for the Gazyva full Prescribing Information, including BOXED WARNINGS, for additional Important Safety Information.
About the German CLL Study Group (GCLLSG)
Founded in 1996 and headed by Michael Hallek, M.D., the GCLLSG has been running various Phase III, Phase II and Phase I trials in chronic lymphocytic leukemia (CLL) with the goal to provide optimal treatment to patients suffering from this disease. Among those were landmark trials like the CLL8 and the CLL11 trials which led to the current standard of care in CLL. For many years, GCLLSG has been aiming to improve not just the treatment of younger and physically fit patients, but also that of elderly and less fit patients. These patients are generally underrepresented in clinical trials although they constitute the majority of CLL patients treated by doctors in daily practice. The GCLLSG is an independent non-profit research organization supported by the German Cancer Aid (Deutsche Krebshilfe). http://www.dcllsg.de.
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.