Genentech’s Obinutuzumab (GA101) Significantly Reduced the Risk of Disease
Progression or Death in People with One of the Most Common Forms of Blood
*Phase III data from the CLL11 study to be presented at the Annual Meeting
of the American Society of Clinical Oncology (ASCO)
*GA101 plus chlorambucil more than doubled the length of time during which
the disease did not get worse vs. chlorambucil alone
*GA101 granted Breakthrough Therapy Designation by U.S. Food and Drug
SOUTH SAN FRANCISCO, Calif. -- May 15, 2013
Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today
announced the first results from CLL11, a Phase III study of the
investigational medicine GA101 which is being conducted in collaboration with
the German CLL Study Group (GCLLSG). The CLL11 study compared the combination
of either GA101 or Rituxan^® (rituximab) and chlorambucil, a standard
chemotherapy, to chlorambucil alone in chronic lymphocytic leukemia (CLL). CLL
is one of the most common forms of blood cancer and in 2013, it is expected
that there will be nearly 5,000 deaths from CLL in the United States. The
CLL11 study included elderly people with previously untreated CLL who were
often not able to tolerate existing aggressive treatment options.
“People with CLL, particularly the elderly and those with additional medical
problems, need new options,” said Sandra Horning, M.D., global head, Clinical
Development Hematology/Oncology. “As a former practicing hematologist, I
believe GA101 has the potential to one day expand treatment options for people
with CLL and we look forward to continuing to work with the FDA and health
authorities around the world in an effort to bring GA101 to those in need.”
GA101 combined with chlorambucil demonstrated a significant 86 percent
reduction in the risk of disease progression, relapse or death. Additionally,
the length of time during which people lived without their disease worsening
(median progression-free survival, PFS) was more than doubled (23 months
compared to 10.9 months, HR=0.14, 95 percent CI 0.09-0.21, p<.0001) when
compared to chlorambucil alone. The full data, including the comparison of
Rituxan plus chlorambucil with chlorambucil alone will be presented in an oral
session at the 49th Annual Meeting of ASCO in Chicago on Tuesday, June 4.
“Roche has played a significant role in revolutionizing the treatment of blood
cancers. With GA101, our aim was to design a unique antibody that kills cancer
cells directly and engages the patient’s own immune cells to help attack the
cancerous cells,” said Pablo Umaña, head of Roche Glycart AG.
GA101 is the first type II anti-CD20 medicine that is glycoengineered, which
means specific sugar molecules in GA101 were modified (using GlycoMAb
technology) to change its interaction with the body’s immune cells with the
goal of helping the immune system remove cancer cells from the body. In
addition, as a type II anti-CD20 antibody, GA101 binds to CD20 with the aim of
killing cancerous cells directly.
Based on the CLL11 data, marketing applications have been submitted to
regulatory authorities including the European Medicines Association (EMA) and
The FDA has granted GA101 Breakthrough Therapy Designation. This designation
is designed to expedite the development and review of medicines intended to
treat serious diseases and to help ensure patients have access to them through
FDA approval as soon as possible.
Genentech will open an Expanded Access Program (EAP) to provide GA101 to
people with CLL under certain circumstances while the company seeks regulatory
About CLL11 Study (BO21004)
CLL11 is a Phase III, multicenter, open-label, randomized three-arm study
investigating the safety and efficacy profile of either GA101 added to
chlorambucil or Rituxan added to chlorambucil compared to chlorambucil alone
in 781 previously untreated people with CLL and comorbidities (589 patients
are included in this analysis and an additional 192 patients have been
enrolled to enable the forthcoming direct comparison of GA101 versus Rituxan
both in combination with chlorambucil). The study was conducted in
collaboration with the GCLLSG. 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. Specifically, the CLL11 trial data to be presented during ASCO showed
*The addition of GA101 to chlorambucil led to a statistically significant
reduction in the risk of disease progression or death of 86 percent
*The median PFS improved by more than a year from 10.9 months for
chlorambucil alone to 23 months for GA101 plus chlorambucil. (see ** in
table 1 below)
*The addition of Rituxan to chlorambucil significantly reduced the risk of
disease progression or death during study follow-up by 68 percent
*Median PFS was 10.8 months for chlorambucil compared to 15.7 months for
Rituxan plus chlorambucil.
*At this time, no formal comparison between the GA101 and Rituxan arms can
be made as the number of PFS events required for that formal analysis has
not yet been reached.
*No new safety signals were detected for either GA101 or Rituxan. The most
common Grade 3-4 adverse events (AEs) for GA101 were infusion-related
reactions (IRRs) and low cell count of certain white blood cells
(neutropenia). The incidence and severity of IRRs decreased dramatically
after the first infusion and no serious IRRs have been reported beyond the
first infusion. The most common AEs are displayed in table 1 below.
*The most common AEs in the Rituxan arm were infections and neutropenia and
are displayed in table 1 below.
Table 1: Summary of key efficacy and safety data
Total Stage 1 Stage 1a Stage1b
N = 589 Chlorambucil GA101 + Chlorambucil Rituxan +
(N=118)* Chlorambucil (N=118)* Chlorambucil
observation time, 13.6 14.5 14.2 15.3
End of treatment 30.2 75.5 30.0 65.9
response rate, %
Complete 0 22.2 0 8.3
Median PFS, 10.9 23.0** 10.8 15.7
HR, CI, p-value 0.14, 0.09-0.21, <.0001 0.32, 0.24-0.44, <.0001
MRD negative in 0% 31% 0% 2%
All Grade 3-4
adverse events 41 67 41 46
Infusion-related - 21*** - 4
Neutropenia 15 34 15 25
Infections 11 6 11 8
* In the chlorambucil-only arm, data cut-off times were different for the two
independent combination analyses which leads to the slightly different results
in the outcomes.
** The percentage of GA101 patients who have not progressed and who have been
observed for longer than the current median PFS time is very small (less than
10%) and therefore as observation time increases, future calculations of
median PFS for the GA101 patients are likely to report different results.
*** No serious (Grade 3-4) IRRs have been reported beyond the first infusion.
About Obinutuzumab (GA101)
GA101 is an investigational medicine that works with the body’s immune system
and is designed to attack cells that have a certain marker on their surface.
GA101 is currently being investigated in a large clinical program, including
multiple head-to-head Phase III studies versus Rituxan in indolent non-Hodgkin
lymphoma (NHL) and diffuse large B-cell lymphoma (DLBCL).
Roche Glycart AG is a wholly-owned, independent research unit, part of Roche
Pharma Research and Early Development.
About Genentech/Roche In Hematology
For more than 20 years, Genentech/Roche 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
In addition to GA101, Genentech/Roche’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
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
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
Joe St. Martin, 650-467-6800
Jen Mills, 650-467-6722
Thomas Kudsk Larsen, 650-467-2016
Karl Mahler, 011 41 61 687 8503
Press spacebar to pause and continue. Press esc to stop.