Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced new, positive data from the second stage of the CLL11 study. This Phase III study, conducted in cooperation with the German CLL Study Group, compared Gazyva™ (obinutuzumab), also known as GA101, in combination with chlorambucil to Rituxan ® (rituximab) in combination with chlorambucil for people with previously untreated chronic lymphocytic leukemia (CLL) and co-existing medical conditions. The data showed that people treated in the Gazyva arm lived nearly a year longer without their disease worsening (progression-free survival, or PFS). For patients in the Gazyva arm, median PFS was 26.7 months compared with 15.2 months for those in the Rituxan arm (HR 0.39, CI 0.31-0.49, p<0.0001). No new safety signals were observed for either Gazyva or Rituxan. The data have been accepted for presentation during the Plenary Scientific Session of the 55th Annual Meeting of American Society of Hematology (Abstract #6). “Gazyva is the result of years of research for patients with chronic lymphocytic leukemia,” said Hal Barron, M.D., chief medical officer and head of Global Product Development. “These new data are important because they showed for the first time that Gazyva significantly extended progression-free survival when directly compared against Rituxan.” Additional data comparing the Gazyva and Rituxan treatment arms showed higher complete response rates (21 percent compared with 7 percent) and a ten-fold increase in the percentage of people achieving minimal residual disease (MRD) negativity (29.4 percent compared with 2.5 percent), which was defined as no detectable disease in the blood at the end of the treatment course. In addition to the Stage 2 data being presented at ASH, an updated analysis from the first stage (Stage 1a) of the CLL11 study, which compared Gazyva in combination with chlorambucil to chlorambucil alone, will also be presented. This analysis showed that people treated with Gazyva in combination with chlorambucil lived longer (overall survival, or OS) compared to chlorambucil alone (HR 0.41, 95 percent CI 0.23-0.74, p=0.002). Given the median observation time of 23 months, median overall survival has not yet been reached in any of the study arms.
On November 1, 2013, Gazyva in combination with chlorambucil became the first medicine with Breakthrough Therapy Designation to receive U.S. Food and Drug Administration (FDA) approval. Roche has also submitted Marketing Authorization Applications to other regulatory authorities around the world, including the European Medicines Agency (EMA).The following data related to Gazyva will be also presented during the ASH annual meeting:
- Safety and Efficacy of Obinutuzumab (GA101) with Fludarabine/Cyclophosphamide (G-FC) or Bendamustine (G-B) in the Initial Therapy of Patients with Chronic Lymphocytic Leukemia (CLL): Results from the Phase Ib GALTON Trial (GAO4779g) (Abstract #523)
- Safety and Efficacy Of Obinutuzumab (GA101) Plus CHOP Chemotherapy In First-Line Advanced Diffuse Large B-Cell Lymphoma: Results From The Phase II GATHER Study (GAO4915g) (Abstract #1820)
- Obinutuzumab (GA101) Plus CHOP or FC in Relapsed/Refractory Follicular Lymphoma: Final Data From the Maintenance phase of the Phase Ib GAUDI Study (BO21000) (Abstract #1814)
|Stage 2 results (investigator assessed) Total N = 663||Gazyva pluschlorambucil N=333||Rituxan pluschlorambucil N=330|
|Overall response rate (ORR), %*||78||65|
|Complete response (CR), %*||21||7|
|Median PFS, months Hazard Ratio, 95 percent Cl, p-value log rank test||26.7#||15.2|
|0.39, 0.31-0.49, p<0.0001|
|Median OS, months HR, Cl, p||NR||NR|
|0.66, 0.41-1.06, p=0.09|
|Minimal residual disease||63/214 [29.4%]||6/243 [2.5%]|
|Grade 3-5 Adverse events, %**||66||47|
|Grade 3-5 Infusion-related reactions, %***||20||4|
|Grade 3-5 Neutropenia (low count of certain white blood cells), %***||33||27|
|Grade 3-5 Infections, %||7||7|
|***||No deaths (grade 5 AE) in these categories|
About GazyvaGazyva is a new monoclonal antibody designed to attach to CD20, a protein found only on B-cells. It attacks targeted cells both directly and together with the body's immune system. Gazyva was discovered by 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 Idec. Gazyva is now approved in combination with chlorambucil for people with previously untreated chronic lymphocytic leukemia and is additionally being investigated in a large clinical program, including multiple head-to-head Phase III studies compared to Rituxan in indolent non-Hodgkin’s lymphoma (NHL) and diffuse large B-cell lymphoma (DLBCL). About The German CLL Study Group (GCLLSG) Founded in 1996 and headed by Professor Michael Hallek, the GCLLSG has been running various Phase I, II and III trials with the goal providing optimal treatment to patients suffering from CLL. This included landmark trials like CLL8, 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 German Cancer Aid (Deutsche Krebshilfe). Gazyva Indication Statement Gazyva is a prescription medicine used with the chemotherapy chlorambucil, to treat chronic lymphocytic leukemia (CLL) in adults who have not had previous CLL treatment. Important Safety Information Patients must tell their doctor right away about any side effects they experience. Gazyva can cause side effects that can become serious or life-threatening including: Hepatitis B Virus (HBV) Reactivation: may cause serious liver problems including liver failure and death. If patients have had hepatitis B or are carriers of HBV, receiving Gazyva could cause the virus to become an active infection again. Patients should not receive Gazyva if they have active HBV liver disease. A patient’s doctor will do blood tests to check for HBV infection prior to treatment and will monitor the patient during and for several months following their treatment. Progressive Multifocal Leukoencephalopathy (PML): a serious brain infection that can lead to severe disability and death and for which there is no known prevention, treatment, or cure. Symptoms can include difficulty thinking, loss of balance, changes in speech or walking, weakness on one side of the body, or blurred or lost vision. Additional possible serious side effects of Gazyva: Patients must tell their doctor right away about any side effects they experience. Gazyva can cause side effects that may become severe or life-threatening, including:
- Infusion Reactions: may occur during or within 24 hours of the infusion. The patient’s doctor should give the patient medicines before their treatment that may help to reduce the risk of an infusion reaction. Symptoms can include hives, rash, itching, facial or oral swelling, sudden cough, shortness of breath, difficulty breathing, weakness, dizziness, feeling faint, racing heart or chest pain.
- Tumor Lysis Syndrome (TLS): TLS is caused by a fast breakdown of cancer cells. TLS may cause an abnormal heartbeat or kidney failure requiring the need for dialysis treatment. The patient’s doctor may do blood tests to check the patient for TLS and give the patient medicines before their treatment to help prevent TLS. Symptoms of TLS may include nausea, vomiting, diarrhea and tiredness.
- Infections: Serious bacterial, fungal and viral infections can occur during and following Gazyva therapy. Symptoms may include fever and cough.
- Low blood cell counts: The patient’s blood cell counts may be monitored during treatment.
Before receiving Gazyva, patients should talk to their doctor about:Immunizations: Before receiving Gazyva therapy, patients must tell their healthcare provider if they have recently received or are scheduled to receive a vaccine. People who are treated with Gazyva should not receive live vaccines. Pregnancy: Patients must tell their doctor if they are pregnant or planning to become pregnant or are breastfeeding. It is not known if Gazyva may harm the patient’s unborn baby or pass into the patient’s breast milk. Women should use birth control while using Gazyva and for 12 months after treatment. Patients must tell their doctor about any side effect that bothers them or that does not go away. 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 full Prescribing Information, including Boxed WARNINGS, for additional Important Safety Information. Rituxan Indications Rituxan is indicated for the treatment of patients with:
- Relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL as a single agent
- Previously untreated follicular, CD20-positive, B-cell NHL in combination with first-line chemotherapy and, in patients achieving a complete or partial response to Rituxan in combination with chemotherapy, as single-agent maintenance therapy
- Non-progressing (including stable disease), low-grade, CD20-positive, B-cell NHL, as a single agent, after first-line CVP chemotherapy
- Previously untreated diffuse large B-cell, CD20-positive NHL in combination with CHOP or other anthracycline-based chemotherapy regimens
- Previously untreated and previously treated CD20-positive CLL in combination with fludarabine and cyclophosphamide (FC)
- Infusion Reactions: may occur during or within 24 hours of the infusion. The patient’s doctor should give the patient medicines before their treatment. Symptoms can include hives, rash, itching, facial or oral swelling, sudden cough, shortness of breath, difficulty breathing, weakness, dizziness, feeling faint, racing heart or chest pain
- Severe Skin and Mouth Reactions: symptoms can include painful sores, ulcers, or blisters on the skin, lips or mouth; peeling skin; rash; or pustules
- Hepatitis B Virus (HBV) Reactivation: may cause serious liver problems including liver failure and death. If patients have had hepatitis B or are carriers of HBV, receiving Rituxan could cause the virus to become an active infection again. Patient should not receive Rituxan if they have active HBV liver disease. The patient’s doctor will do blood tests to check for HBV infection prior to treatment and will monitor the patient during and for several months following their treatment
- Progressive Multifocal Leukoencephalopathy (PML): a rare, serious brain infection that can lead to severe disability and death and for which there is no known prevention, treatment or cure. Symptoms can include difficulty thinking, loss of balance, changes in speech or walking, weakness on one side of the body or blurred or lost vision
- Tumor Lysis Syndrome (TLS): may cause kidney failure and the need for dialysis treatment, abnormal heart rhythm and can lead to death. The patient’s doctor may give the patient medicines before their treatment to help prevent TLS
- Serious Infections: can happen during and after treatment and can lead to death. These infections may be bacterial, fungal or viral. Symptoms can include fever; cold or flu symptoms; earache or headache; pain during urination; white patches in the mouth or throat; cuts or scrapes that are red, warm, swollen or painful
- Heart Problems: symptoms can include chest pain and irregular heartbeats that may require treatment. The patient’s doctor may need to stop their treatment
- Kidney Problems: the patient’s doctor should do blood tests to check how well the patient’s kidneys are working
- Stomach and Serious Bowel Problems: can include blockage or tears in the bowel that can lead to death. Stomach area pain during treatment can be a symptom
- Low Blood Cell Counts: the patient’s blood cell counts may be monitored during treatment
Patients must tell their doctor if they are pregnant, plan to become pregnant or are breastfeeding. It is not known if Rituxan may harm the patient’s unborn baby or pass into the patient’s breast milk. Women should use birth control while using Rituxan and for 12 months after treatment.Patients must tell their doctor about any side effect that bothers them or that does not go away. These are not all of the possible side effects of Rituxan. For more information, patients should ask their doctor or pharmacist. 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 see the Rituxan full Prescribing Information, including Most Serious Side Effects, for additional important safety information at http://www.Rituxan.com. 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 cancers of the blood. In addition to Gazyva, Genentech’s pipeline of potential hematology medicines includes two antibody-drug conjugates (anti-CD79b [RG7596] and anti-CD22 [RG7593]), a small molecule antagonist of MDM2 (RG7112) and in collaboration with AbbVie, a small molecule BCL-2 inhibitor (RG7601/GDC-0199/ABT-199). About Genentech Founded more than 35 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious or 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.