-
Diffuse large B-cell lymphoma
is an aggressive type of blood cancer that typically becomes harder
to treat each time it returns
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Polatuzumab vedotin has shown
significant potential to improve outcomes in people living with
this disease
Basel, 19 February 2019 - Roche (SIX: RO, ROG;
OTCQX: RHHBY) today announced that the US Food and Drug
Administration (FDA) has accepted the company's Biologics License
Application (BLA) and granted Priority Review for polatuzumab
vedotin in combination with bendamustine plus Rituxan® (rituximab)
(BR) for the treatment of people with relapsed or refractory (R/R)
diffuse large B-cell lymphoma (DLBCL). The FDA is expected to make
a decision on approval by 19 August 2019.
"Polatuzumab vedotin, a potential first-in-class antibody drug
conjugate, in combination with bendamustine and Rituxan, improved
clinical outcomes including survival in some people with relapsed
or refractory diffuse large B-cell lymphoma compared to
bendamustine and Rituxan alone," said Sandra Horning, MD, Roche's
Chief Medical Officer and Head of Global Product Development. "We
are working with the FDA to bring this important new option to
patients with this aggressive disease as quickly as
possible."
The BLA is based on results of the GO29365 study, which showed that
polatuzumab vedotin plus BR improved median overall survival
compared to BR alone (12.4 vs. 4.7 months, HR=0.42; 95% CI
0.24-0.75; exploratory endpoint), in people with R/R DLBCL not
eligible for a haematopoietic stem cell transplant. The study also
showed that 40% of people treated with polatuzumab vedotin plus BR
achieved a complete response (CR), while only 18% of people treated
with BR alone achieved a CR (primary endpoint, as measured by
positron emission tomography; CR rates assessed by independent
review committee). A CR means no cancer could be detected at that
time.
Priority Review designation is granted to medicines that the FDA
considers to have the potential to provide significant improvements
in the safety and effectiveness of the treatment, prevention or
diagnosis of a serious disease. Polatuzumab vedotin was also
granted Breakthrough Therapy Designation by the FDA and PRIME
(PRIority MEdicines) designation by the European Medicines Agency
for the treatment of people with R/R DLBCL in 2017. Breakthrough
Therapy Designation is designed to expedite the development and
review of medicines intended to treat a serious condition with
preliminary evidence that indicates they may demonstrate
substantial improvement over existing therapies.
About the GO29365 study
GO29365 is a global, phase Ib/II randomised study evaluating the
safety, tolerability and activity of polatuzumab vedotin in
combination with bendamustine and Rituxan (rituximab) or Gazyva
(obinutuzumab) in relapsed or refractory (R/R) follicular lymphoma
or diffuse large B-cell lymphoma (DLBCL). The phase II stage
randomised 80 patients with heavily pre-treated R/R DLBCL to
receive either bendamustine plus Rituxan (BR), or BR in combination
with polatuzumab vedotin. Patients enrolled had received a median
of two prior therapies (a range of 1-7 prior therapies in the
polatuzumab vedotin arm and range of 1-5 prior therapies in the BR
alone arm). The primary endpoint was complete response (CR) at the
end of treatment, as measured by positron emission tomography (PET)
and assessed by an independent review committee (IRC). Secondary
endpoints included objective response (OR; CR and partial response,
PR) by investigator assessment and best objective response at the
end of treatment by investigator and IRC assessment. Exploratory
endpoints included duration of response (DOR), progression-free
survival (PFS), event-free survival (EFS) and overall survival
(OS).
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40% of people treated with polatuzumab vedotin
plus BR achieved a CR while only 18% of people treated with BR
alone achieved a CR (primary endpoint, as measured by PET; CR rates
assessed by IRC). A CR means no cancer could be detected at that
time.
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Polatuzumab vedotin in combination with BR
showed a median OS of over one year compared to the BR arm (12.4
vs. 4.7 months, HR=0.42; 95% CI 0.24-0.75), in people with R/R
DLBCL not eligible for a hematopoietic stem cell transplant. OS was
an exploratory endpoint.
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Polatuzumab vedotin plus BR increased median PFS
and led to a 66% reduction in risk of disease worsening or death
compared to BR alone (median PFS: 7.6 months vs. 2.0 months;
HR=0.34; 95% CI 0.20-0.57).
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Patients treated with polatuzumab vedotin plus
BR showed a longer time between first response to treatment and
disease worsening than those receiving BR alone (investigator
assessed median DOR: 10.3 months vs. 4.1 months; HR=0.44).
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Updated safety results are similar to those
previously described, with infections and cytopenias remaining the
most common Grade 3-4 adverse events (AEs). Polatuzumab vedotin
plus BR had higher rates of Grade 3-4 cytopenias compared to BR,
however, infection and transfusion rates remained similar between
arms.
About polatuzumab vedotin
Polatuzumab vedotin is a first-in-class anti-CD79b antibody drug
conjugate (ADC) currently being investigated for the treatment of
several types of non-Hodgkin lymphoma (NHL). The CD79b protein is
highly specific and expressed in the majority of types of B-cell
NHL, making it a promising target for the development of new
therapies.1, 2
Polatuzumab vedotin binds to CD79b and destroys these B-cells
through a targeted approach, which is thought to minimise the
effects on normal cells while maximising tumour cell
death.3, 4
Polatuzumab vedotin is being developed by Roche utilising Seattle
Genetics ADC technology.
About diffuse large B-cell lymphoma
Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of
non-Hodgkin lymphoma (NHL), accounting for about one in three cases
of NHL.5 DLBCL is an
aggressive (fast-growing) type of NHL, which is generally
responsive to treatment in the frontline.6 However, as
many as 40% of patients will relapse, at which time salvage therapy
options are limited and survival is short.1, 4
Approximately 150,000 people worldwide are estimated to be
diagnosed with DLBCL each year.7
About Roche in haematology
For more than 20 years, Roche has been developing medicines that
redefine treatment in haematology. Today, we are investing more
than ever in our effort to bring innovative treatment options to
people with diseases of the blood. In addition to approved
medicines MabThera®/Rituxan® (rituximab), Gazyva®/Gazyvaro®
(obinutuzumab), and Venclexta®/Venclyxto® (venetoclax) in
collaboration with AbbVie, Roche's pipeline of investigational
haematology medicines includes Tecentriq® (atezolizumab), an
anti-CD79b antibody drug conjugate (polatuzumab vedotin/RG7596) and
a small molecule which inhibits the interaction of MDM2 with p53
(idasanutlin/RG7388). Roche's dedication to developing novel
molecules in haematology expands beyond malignancy, with the
development of Hemlibra® (emicizumab), a bispecific monoclonal
antibody for the treatment of haemophilia A.
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
law.
References
[1] Dornan D, et al. Therapeutic potential of an anti-CD79b
antibody-drug conjugate, anti-CD79b-vc-MMAE, for the treatment of
non-Hodgkin lymphoma. Blood 2009; 114:2721-2729.
[2] Pfeifer M, et al. Anti-CD22 and anti-CD79B antibody drug
conjugates are active in different molecular diffuse large B-cell
lymphoma subtypes. Leukemia 2015; 29:1578-1586
[3] Ducry L, Stump B. Antibody-drug conjugates: linking cytotoxic
payloads to monoclonal antibodies.
Bioconjug Chem. 2010; 21:5 - 13.
[4] ADC Review. What are antibody-drug conjugates? [Internet; cited
February 2019].
Available from:
https://adcreview.com/adc-university/adcs-101/antibody-drug-conjugates-adcs/
[5] Lyon, France. World Health Organization Classification of
Tumors of Haematopoietic and Lymphoid Tissues. IARC Press;
2008.
[6] Maurer, JM et al. Event-free survival at 24 months is a robust
end point for disease-related outcome in diffuse large B-cell
lymphoma treated with immunochemotherapy. J Clin Oncol 2014;
32:1066-73.
[7] Numbers derived from GLOBOCAN 2018: Estimated cancer incidence,
mortality and prevalence worldwide in 2018. [Internet; cited 2018
May]. Available from: http://globocan.iarc.fr.
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Relations
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- Patrick Barth
- Ulrike Engels-Lange
- Simone Oeschger
- Anja von Treskow
20190219-MR-FDA grants Priority
Review to Roche’s polatuzumab vedotin