-
Fixed 12-month treatment with
Venclexta plus Gazyva significantly reduced risk of disease
progression or death by 67% compared to a current
standard-of-care
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Approval for expanded use of
Venclexta offers more adults with chronic lymphocytic leukaemia a
new treatment option
Basel, 16 May 2019 -
Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that the US Food
and Drug Administration (FDA) has approved Venclexta® (venetoclax)
in combination with Gazyva® (obinutuzumab) for the treatment of
people with previously untreated chronic lymphocytic leukaemia
(CLL) or small lymphocytic lymphoma (SLL).
"Venclexta plus Gazyva is the only chemotherapy-free option of
fixed duration that provides durable responses to help people live
longer without progression of their disease, compared to a
standard-of-care," said Sandra Horning, MD, Roche's Chief Medical
Officer and Head of Global Product Development. "Today's approval
represents our long-standing commitment to helping people with
blood cancers throughout the course of their disease, and we are
excited to provide this new option for untreated chronic
lymphocytic leukaemia."
The approval is based on the results of the randomised phase III
CLL14 study, which evaluated 12-month, fixed-duration treatment
with Venclexta plus Gazyva compared to Gazyva plus chlorambucil.
Results showed the combination of Venclexta plus Gazyva produced a
durable and significant reduction in the risk of disease worsening
or death (progression-free survival [PFS], as assessed by
Independent Review Committee) by 67% compared to Gazyva plus
chlorambucil, a current standard-of-care (HR=0.33; 95% CI
0.22-0.51; p<0.0001). Venclexta plus Gazyva showed deep and
clinically meaningful responses characterised by a higher rate of
minimal residual disease (MRD)-negativity in the bone marrow
compared to Gazyva plus chlorambucil (MRD-negativity of 57% vs.
17%) and peripheral blood (MRD-negativity of 76% vs. 35%).
MRD-negativity means no cancer can be detected using a specific and
highly sensitive test, defined as less than one CLL cell in 10,000
white blood cells.
Results of the study will be presented at the American Society of
Clinical Oncology Annual Meeting in June 2019. The CLL14 study is
being conducted in cooperation with the German CLL Study Group
(GCLLSG), headed by Michael Hallek, MD, University of
Cologne.
The most common adverse reactions with Venclexta plus Gazyva were
low white blood cell count, diarrhoea, fatigue, nausea, low red
blood cell count, and upper respiratory tract infection.
The FDA rapidly reviewed and approved the supplemental New Drug
Application (sNDA) under the FDA's Real-Time Oncology Review (RTOR)
and Assessment Aid pilot programmes. This is the second regimen of
Roche medicines approved under the RTOR pilot programme, which is
exploring a more efficient review process to ensure safe and
effective treatments are available to patients as early as
possible. The sNDA was also granted Priority Review, a designation
given to medicines that the FDA has determined to have the
potential to provide significant improvements in the treatment,
prevention or diagnosis of a disease. The FDA previously granted
Breakthrough Therapy Designation for Venclexta in combination with
Gazyva for the treatment of previously untreated CLL with
co-existing medical conditions. Additional submissions of the CLL14
data to health authorities around the world are ongoing.
Venclexta is being developed by AbbVie and Roche. It is jointly
commercialised by AbbVie and Genentech, a member of the Roche
group, in the US and commercialised by AbbVie outside of the
US.
About the CLL14 Study
CLL14
(NCT02242942) is a randomised phase III study evaluating the
combination of fixed-duration Venclexta plus Gazyva compared to
Gazyva plus chlorambucil in patients with previously untreated
chronic lymphocytic leukaemia (CLL) and co-existing medical
conditions. 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 plus chlorambucil followed by an
additional six-month duration of chlorambucil (Arm B). Arm A
started with an initial cycle of Gazyva followed by a five-week
Venclexta dose ramp-up to help reduce tumour burden. 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 (OR), complete response (with or without
complete blood count recovery, CR/CRi), overall survival (OS),
duration of response (DOR), event-free survival (EFS), time to next
CLL treatment (TTNT) and safety. The CLL14 study is being conducted
in cooperation with the German CLL Study Group (GCLLSG), headed by
Michael Hallek, MD, University of Cologne.
CLL14 Study Results |
Treatment arm |
Venclexta + Gazyva
(n=216) |
Gazyva +
chlorambucil
(n=216) |
Progression Free Survival (PFS)a |
Median PFS |
Independent Review Committee (IRC): Not reached |
IRC: Not reached |
Number of Events, n (%) |
29 (13) |
79 (37) |
|
IRC: HR = 0.33 (95% CI 0.22-0.51), p<0.0001 |
Response Rates |
ORR % (95% CI) |
85 (79-89) |
71 (65-77) |
p value |
0.0007 |
|
CR/CRi |
50 |
23 |
p value |
<0.0001 |
|
Minimal Residual Disease (MRD)b |
MRD-negative, %, bone marrow (95% CI) |
57 (50-64) |
17 (12-23) |
p value |
<0.0001 |
MRD-negative, % peripheral blood (95% CI) |
76 (69-81) |
35 (29-42) |
p value |
<0.0001 |
Overall Survival (OS) |
OS |
Not reached |
Not reached |
a Approval based on secondary endpoint of PFS evaluated by
IRC; data at median follow-up of 28 months
b Data at 3-months following end of combination
treatment
The most common adverse reactions with
Venclexta plus Gazyva were low white blood cell count, diarrhoea,
fatigue, nausea, low red blood cell count, and upper respiratory
tract infection.
About Venclexta/Venclyxto (venetoclax)
Venclexta/Venclyxto 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
tumours, BCL-2 builds up and prevents cancer cells from dying or
self-destructing, a process called apoptosis. Venclexta/Venclyxto
blocks the BCL-2 protein and works to restore the process of
apoptosis.
Venclexta/Venclyxto is being developed by AbbVie and Roche. It is
jointly commercialised by AbbVie and Genentech, a member of the
Roche Group, in the US and commercialised by AbbVie, under the
brand name Venclyxto, outside of the US. Together, the companies
are committed to research with Venclexta/Venclyxto, which is
currently being studied in clinical trials across several types of
blood and other cancers.
In the US, Venclexta has been granted five Breakthrough Therapy
Designations by the US Food and Drug Administration: one for
previously untreated CLL, two for relapsed or refractory CLL and
two for previously untreated acute myeloid leukaemia.
About Gazyva/Gazyvaro (obinutuzumab)
Gazyva/Gazyvaro is an engineered monoclonal antibody
designed to attach to CD20, a protein expressed on certain B cells,
but not on stem cells or plasma cells. Gazyva/Gazyvaro is designed
to attack and destroy targeted B-cells both directly and together
with the body's immune system. Gazyva is marketed as Gazyvaro in
the EU and Switzerland.
Gazyva/Gazyvaro is currently approved in more than 90 countries in
combination with chlorambucil for people with previously untreated
chronic lymphocytic leukaemia, in more than 80 countries in
combination with bendamustine for people with certain types of
previously treated follicular lymphoma and in more than 70
countries in combination with chemotherapy for previously untreated
follicular lymphoma.
Additional combination studies investigating Gazyva/Gazyvaro with
other approved or investigational medicines, including cancer
immunotherapies and small molecule inhibitors, are underway across
a range of blood cancers.
About the German CLL Study Group
(GCLLSG)
Founded in 1996 and headed by Michael Hallek, MD, the GCLLSG has
been running various phase III, phase II and phase I trials in
chronic lymphocytic leukaemia (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 organisation supported by the German Cancer Aid
(Deutsche Krebshilfe) www.dcllsg.de.
About Roche in haematology
Roche has been
developing medicines for people with malignant and non-malignant
blood diseases for over 20 years; our experience and knowledge in
this therapeutic area runs deep. Today, we are investing more than
ever in our effort to bring innovative treatment options to
patients across a wide range of haematologic diseases. Our approved
medicines include MabThera®/Rituxan® (rituximab), Gazyva®/Gazyvaro®
(obinutuzumab), Venclexta®/Venclyxto® (venetoclax) in collaboration
with AbbVie, and Hemlibra® (emicizumab). Our pipeline of
investigational haematology medicines includes polatuzumab vedotin,
an anti-CD79b antibody drug conjugate; idasanutlin, a small
molecule which inhibits the interaction of MDM2 with p53; T-cell
engaging bispecific antibodies targeting both CD20 and CD3, and
Tecentriq® (atezolizumab), a monoclonal antibody designed to bind
with PD-L1. Our scientific expertise, combined with the breadth of
our portfolio and pipeline, also provides a unique opportunity to
develop combination regimens that aim to improve the lives of
patients even further.
About Roche
Roche is a
global pioneer in pharmaceuticals and diagnostics focused on
advancing science to improve people's lives. The combined strengths
of pharmaceuticals and diagnostics under one roof have made Roche
the leader in personalised healthcare - a strategy that aims to fit
the right treatment to each patient in the best way
possible.
Roche is the world's largest biotech company, with truly
differentiated medicines in oncology, immunology, infectious
diseases, ophthalmology and diseases of the central nervous system.
Roche is also the world leader in in vitro diagnostics and
tissue-based cancer diagnostics, and a frontrunner in diabetes
management.
Founded in 1896, Roche continues to search for better ways to
prevent, diagnose and treat diseases and make a sustainable
contribution to society. The company also aims to
improve patient access to medical innovations by working with
all relevant stakeholders. Thirty medicines developed by Roche are
included in the World Health Organization Model Lists of Essential
Medicines, among them life-saving antibiotics, antimalarials and
cancer medicines. Moreover, for the tenth consecutive year, Roche
has been recognised as the most sustainable company in the
Pharmaceuticals Industry by the Dow Jones Sustainability Indices
(DJSI).
The Roche Group, headquartered in Basel, Switzerland, is active in
over 100 countries and in 2018 employed about 94,000 people
worldwide. In 2018, Roche invested CHF 11 billion in R&D and
posted sales of CHF 56.8 billion. Genentech, in the United
States, is a wholly owned member of the Roche Group. Roche is the
majority shareholder in Chugai Pharmaceutical, Japan. For more
information, please visit www.roche.com.
All trademarks used or mentioned in this release are protected by
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Roche Group Media Relations
Phone: +41 61 688 8888 / e-mail:
media.relations@roche.com
- Nicolas Dunant (Head)
- Patrick Barth
- Ulrike Engels-Lange
- Simone Oeschger
- Anja von Treskow
190516_CLL14 Global FDA
approval_EN