13423/ Genentech's Obinutuzumab (GA101) Delayed Disease Progression Longer Than Rituxan® in People with One of the Most Common Forms of Blood Cancer
• Phase III CLL11 study showed GA101 plus chlorambucil, a chemotherapy, was superior to Rituxan plus chlorambucil in helping people with previously untreated chronic lymphocytic leukemia live longer without their disease worsening
• Final data from the CLL11 study will be submitted to the American Society of Hematology's 55th Annual Meeting in December 2013
At a pre-planned interim analysis, an independent data monitoring committee determined that the study met its primary endpoint showing that GA101 plus chlorambucil helped people live significantly longer without their disease worsening (progression-free survival; PFS) compared to Rituxan® (rituximab) plus chlorambucil. The CLL11 study is being conducted in cooperation with the German CLL Study Group (GCLLSG). These final data were reached well ahead of the target completion date in 2014 as a result of the magnitude of difference seen between the two study arms. No new safety signals for GA101 or Rituxan were identified in this analysis, and adverse events were similar to those observed in the first stage of the study which was previously reported earlier this year.
"The positive final results from the CLL11 study show the promise that GA101 could hold for people with CLL," said Hal Barron, M.D., chief medical officer and head, Global Product Development. "It is important to explore the potential of this medicine in other types of blood cancer, and our broad development program includes studies in aggressive and indolent lymphoma that compare GA101 with Rituxan."
GA101 is the first type II anti-CD20 medicine that is glycoengineered, which means specific sugar molecules in GA101 were modified to change its interaction with the body's immune cells. This modification creates a unique antibody that is designed to act as an immunotherapy, engaging the patient's own immune system to help attack the cancerous cells. In addition, GA101 binds to CD20 with the aim of inducing direct cell death.
These data will be submitted for consideration to the 55th Annual Meeting of the American Society of Hematology (ASH) in New Orleans, which is taking place December 7-10, 2013.
Based on an earlier analysis (Stage 1) of the CLL11 study, marketing applications for GA101 were submitted to regulatory authorities including the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) in April 2013. Due to the significance of the positive trial results and the serious and life threatening nature of CLL, the FDA granted the GA101 application both Breakthrough Therapy Designation and Priority Review.
About Obinutuzumab (GA101)
GA101 is the first investigational type II, glycoengineered medicine designed to attack cells that have a certain marker (CD20) on their surface. It attacks targeted cells both directly and together with the body's immune system. GA101 is currently being investigated in a large clinical program, including multiple head-to-head Phase III studies versus Rituxan in indolent non-Hodgkin¿s lymphoma (NHL) and diffuse large B-cell lymphoma (DLBCL).
In the U.S., GA101 is being developed and will be commercialized in collaboration with Biogen Idec.
About the CLL11 Study
CLL11 is a Phase III, multicenter, open-label, randomized three-arm study investigating the efficacy and safety profile of either GA101 plus chlorambucil or Rituxan plus chlorambucil compared to chlorambucil alone in 781 previously untreated people with CLL and co-existing medical conditions who are in need of therapy. The study included two stages of analysis.
• Stage 1 included 589 patients and compared GA101 plus chlorambucil to chlorambucil alone and Rituxan plus chlorambucil to chlorambucil alone. Stage 1 results were reported earlier this year and showed that GA101 plus chlorambucil doubled the time people lived without their disease worsening compared to chlorambucil alone (23 months compared to 10.9 months, HR=0.14, 95 percent CI 0.09-0.21, p<.0001).
• Stage 2 (announced today) enrolled an additional 192 patients to enable the final direct comparison of GA101 versus Rituxan, both in combination with chlorambucil.
The primary endpoint of the study was PFS with secondary endpoints including overall response rate (ORR), overall survival (OS), disease-free survival (DFS), minimal residual disease (MRD) and safety profile.
About the German CLL Study Group (GCLLSG)
Founded in 1996 and headed by Dr. Michael Hallek, the GCLLSG has been running various Phase III, Phase II and Phase I trials in CLL with the goal to provide optimal treatment to patients suffering from this disease. Among those were landmark trials like the CLL8 trial 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).
About FDA Breakthrough Therapy Designation and Priority Review
FDA 'Breakthrough Therapy Designation' is designed to expedite the development and review of medicines intended to treat serious and life threatening diseases and to help ensure people have access to them through FDA approval with a shorter review time. A priority review designation is granted to medicines that the FDA believes have the potential to provide significant improvements in the treatment, prevention or diagnosis of a disease.
About Genentech in Hematology
For more than 20 years, Genentech has been developing medicines that 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 GA101, 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).
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 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 rituxan.com/.
Founded more than 30 years ago, Genentech (gene.com) 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.