Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced positive results from Stage 1 of CLL11, a Phase III randomized study to investigate the efficacy and safety profile of the investigational medicine obinutuzumab (GA101) plus chlorambucil chemotherapy compared with chlorambucil alone in people with previously untreated chronic lymphocytic leukemia (CLL). An improvement in progression-free survival (PFS) was achieved as GA101 plus chlorambucil significantly reduced the risk of disease worsening or death compared to chlorambucil alone.
“The improvement in progression-free survival seen with GA101 is encouraging for people with CLL, a chronic illness of older people for which new treatment options are needed,” said Hal Barron, M.D., chief medical officer and head, Global Product Development. “GA101 demonstrates our ongoing commitment to the research and development of new medicines for this disease.”
GA101 has been specifically designed as the first glycoengineered, type 2 anti-CD20 monoclonal antibody in development for B-cell malignancies. In pre-clinical development, GA101 has shown evidence of increased direct cell killing and antibody-dependent cellular cytotoxicity (ADCC). As a result, GA101’s clinical development program is designed to assess whether or not it is superior to Rituxan® (rituximab) in CLL and non-Hodgkin’s lymphoma (NHL).
CLL11 is a three-arm study that compares GA101 plus chlorambucil to Rituxan plus chlorambucil or chlorambucil alone. The study includes two separate stages. Stage 1 evaluated GA101 plus chlorambucil to chlormabucil alone, and included a pre-planned PFS futility analysis comparing GA101 plus chlorambucil to Rituxan plus chlorambucil. The goal of this futility analysis was to evaluate the likelihood that the study would meet its pre-specified endpoint criteria during Stage 2 analysis - improved efficacy (PFS) in the direct comparison of GA101 plus chlorambucil to Rituxan plus chlorambucil. The independent Data and Safety Monitoring Board (DSMB) assessment concluded that Stage 2 of the study should continue until its final analysis. No new safety events were reported for the GA101 or Rituxan containing arms in the study up to the time of this analysis.
Data from CLL11 will be submitted for presentation at an upcoming medical meeting and submitted to European regulatory authorities and the U.S. Food and Drug Administration (FDA) for potential approval.
About CLL11 (BO21004)
CLL11 is a Phase III, multicenter, open-label, randomized three-arm study investigating the safety and efficacy profile of GA101 plus chlorambucil compared to Rituxan plus chlorambucil or chlorambucil alone in nearly 800 previously untreated people with CLL and coexisting medical conditions. The study is conducted in close collaboration with the German CLL Study Group (DCLLSG). The primary endpoint of the study is PFS with secondary endpoints including overall response rate (ORR), overall survival (OS), disease free survival (DFS), molecular remission and safety profile.
About Hematological Malignancies
Hematological malignancies are cancers of the blood and include CLL, indolent NHL and diffuse large B-cell lymphoma (DLBCL). In 2013, it is expected that there will be nearly 19,020 annual deaths from NHL and nearly 4,580 annual deaths from CLL in the United States.
The current standard of care in CD20-positive hematological malignancies is Rituxan in combination with chemotherapy or as a single agent.
In addition to GA101, our pipeline of potential hematology medicines includes two antibody-drug conjugates (anti-CD79b [RG7596] and anti-CD22 [RG7593]), a small molecule BCL-2 inhibitor (RG7601) and a small molecule antagonist of MDM2 (RG7112).
About Obinutuzumab (GA101)
GA101 is Genentech’s most advanced investigational medicine in development for hematological malignancies (cancers which affect the blood, bone marrow and lymph nodes). GA101 targets CD20 proteins found on B-cells, and is designed to result in cell death.
GA101 is the first glycoengineered, type 2 anti-CD20 monoclonal antibody in development for B-cell malignancies. GA101 is currently being investigated in multiple clinical trials, including head-to-head trials versus Rituxan.
Rituxan is a therapeutic antibody that binds to a specific protein called CD20 found on the surface of cancerous and normal B-cells. In CLL, NHL and rheumatoid arthritis (RA), Rituxan works with the body's own immune system to eliminate marked CD20-positive B-cells. Stem cells (those cells that give rise to B-cells) in bone marrow do not have the CD20 protein. B-cells usually regenerate after Rituxan treatment and return to normal levels in about 12 months for most patients.
Rituxan, discovered by Biogen Idec, first received FDA approval in November 1997 for the treatment of relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL as a single agent. It was approved in the European Union under the trade name MabThera in June 1998.
Rituxan® (Rituximab) 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)
Rituxan is not recommended for use in patients with severe, active infections.
Important Safety Information:
Rituxan can cause serious side effects that can lead to death, including: infusion reactions, tumor lysis syndrome (kidney failure due to fast breakdown of cancer cells), severe skin and mouth reactions, and progressive multifocal leukoencephalopathy (a rare, serious brain infection).
Rituxan has also been associated with serious and life-threatening side effects, including: the return of active hepatitis B virus infection with sudden and serious liver problems including liver failure, and death, other serious infections that can lead to death, heart problems, kidney problems, and stomach and serious bowel problems including blockage and tears in the bowel, that can sometimes lead to death.
The most common side effects of Rituxan seen in patients with NHL were infusion reactions, fever, chills, low white blood cells, infections, body aches, and tiredness. The most common side effects of Rituxan in patients with CLL were infusion reactions and low white blood cells. Patients should talk to their doctor about their medical history before starting treatment with Rituxan.
Patients should 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 with Rituxan.
Report side effects to the FDA at (800) FDA-1088 or http://www.fda.gov/medwatch.Patients and caregivers may also report side effects to Genentech at (888) 835-2555.
Patients should read the Rituxan Full Prescribing Information including Boxed WARNINGS, and the Medication Guide at http://www.rituxan.com.
Founded more than 30 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.