New Results add to Growing Body of Evidence That Support Bendamustine-rituximab (B-R) Combination as First-Line Treatment in

           New Results add to Growing Body of Evidence That Support
 Bendamustine-rituximab (B-R) Combination as First-Line Treatment in Patients
       With Indolent non-Hodgkin (iNHL) and Mantle Cell Lymphomas (MCL)

  PR Newswire

  CAMBRIDGE, England, December 11, 2012

CAMBRIDGE, England, December 11, 2012 /PRNewswire/ --

FOR MEDICAL MEDIA ONLY – NOT INTENDED FOR FRENCH MEDIA

Data demonstrate superior patient outcomes with B-R in first-line treatment of
iNHL and MCL, compared with current standard of care

Five sets of new data analyses presented this week at the 54 ^th annual
meeting of the American Society of Hematology (ASH) in Atlanta, Georgia, show
that a first-line treatment regimen of bendamustine plus rituximab (B-R)
results in superior patient outcomes compared with current standard of care,
CHOP-R/CVP-R, in patients with indolent non-Hodgkin lymphomas (iNHL) and
mantle cell lymphomas (MCL). ^[1] ^, ^[2] ^, ^[3] ^, ^[4] ^, ^[5]

A sub-analysis of the StiL NHL 1-2003 Study, demonstrated significantly
prolonged progression free survival (PFS) and overall survival (OS) for iNHL
and MCL patients who achieved a complete response (CR) compared with a partial
response (PR), irrespective of whether they received B-R or CHOP-R treatment.
^[ ^1 ^] A CR was observed in a higher proportion of patients treated with B-R
(39.8%) vs. those treated with CHOP-R (30.0%). ^[ ^1 ^]

Furthermore, when comparing the two treatment arms, first-line treatment with
B-R resulted in superior PFS compared to CHOP-R, regardless of the quality of
response: ^[ ^1 ^]

  *For patients in CR, median PFS exceeded the five year evaluation point
    following B-R treatment, compared to 53.7 months for patients treated with
    CHOP-R (p=0.0204) ^[ ^1 ^]
  *In patients achieving PR, treatment with B-R resulted in a median PFS of
    57.2 months versus 30.9 months with CHOP-R (p=0.0002) ^[ ^1 ^]

Previously presented results from the StiL NHL 1-2003 Study demonstrated a
significant benefit in progression-free survival (PFS) as well as improved
tolerability for B-R compared with CHOP-R. ^[ ^6] , ^[ ^1 ^]

In another study presented at ASH, the Bright study, treatment with B-R was
shown to produce a non-inferior CR rate compared to CHOP-R/CVP-R in patients
with advanced iNHL and MCL (31% B-R vs. 25% CHOP-R/CVP-R, p=0.0225), meeting
the primary objective of the study. ^[ ^2 ^] Additionally, the study
demonstrated a significantly higher CR rate in the MCL subgroup of patients
(51% vs. 24%, p=0.018). ^[ ^2 ^] Response assessments were performed by an
independent review committee.

A third new analysis provided results on the quality of life (QoL) of
previously untreated iNHL and MCL patients on B-R treatment, compared to those
on CHOP-R/CVP-R treatment, from the Bright study. Results showed that B-R
treatment provided improved patient QoL scores for most aspects of functioning
and symptoms. ^[ ^3 ^] Furthermore, B-R significantly improved global health
status (GHS)/QoL compared to the standard of care CHOP-R/CVP-R (3.6 vs. -5.1
respectively, p=0.0005) in these patients. ^[ ^3 ^]

"Over the last year we have seen an increasingly compelling body of evidence
presented that demonstrates bendamustine's potential as a new cornerstone
chemotherapy for the first-line treatment of all iNHL and MCL," said J.G.
Gribben, Professor of Medical Oncology, St. Bartholomew's Hospital, Queen
Mary's School of Medicine, University of London. "These results not only
demonstrate similar complete response rates compared with current standards of
care, but also that the simplified treatment regimen of bendamustine plus
rituximab leads to improved progression-free survival and quality of life with
decreased toxicity for patients fighting indolent non-Hodgkin lymphoma."

Two further studies provide additional supporting evidence for the use of B-R
in first-line iNHL:

  *A review of 645 German patients receiving systemic first-line treatment
    for iNHL in the clinical registry on lymphoid neoplasms (TLN Registry)
    suggests B-R is already the number one chemotherapy cornerstone choice in
    Germany for iNHL. ^[ ^4 ^] B-R was the first-line treatment in 66% of
    cases, compared to just 16% for CHOP-R. ^[ ^4 ^]
  *The first data presented from the MAINTAIN trial, showed B-R to be
    effective as a treatment for Waldenström's Macroglobulinemia, a rare
    subtype of iNHL. ^[ ^5 ^] , ^[7] B-R treatment achieved an overall
    response rate of 86%, with no uncommon toxicities observed during B-R
    induction. ^[ ^5 ^] The MAINTAIN trial was initiated to investigate the
    impact of following B-R first-line induction with rituximab maintenance, a
    technique that has already been shown to improve PFS in previously
    untreated Follicular lymphoma, the most common form of iNHL. ^[ ^5 ^] , ^[
    ^7 ^] , ^[8]

A record number of abstracts, 43 in total, announcing the results of studies
involving bendamustine are being presented at the ASH annual meeting,
demonstrating renewed interest in this molecule as a chemotherapy partner for
novel therapies across a number of B-cell malignancies, including iNHL and
MCL.

"Data from the StiL NHL 1-2003 study have been submitted for a licence
variation and are currently under assessment by the regulatory authorities,"
said Professor Pier Luigi Zinzani of the Institute of Hematology and Medical
Oncology, University of Bologna. "The volume of bendamustine abstracts being
presented at ASH this year also indicates the potential role of this treatment
in novel combinations and across multiple different malignancies.
Fundamentally, bendamustine plus rituximab offers an alternative to existing
more toxic chemotherapy regimens, something that is desperately needed by the
cancer community."

NHL is the tenth most common cancer worldwide and figures from 2008 indicate
that there are an estimated 356,000 new cases diagnosed every year, comprising
two out of five haematological cancers. ^[9] iNHL represents 40% of all NHL
subtypes. ^[10] The estimated average incidence of NHL in 2008 in the European
Union is 10.8 per 100,000. ^[ ^9 ^], ^[11]

                              -Notes to Editors-

About Mundipharma

The Mundipharma network of independent associated companies consists of
privately owned companies and joint ventures covering the world's
pharmaceutical markets. These companies are committed to bringing to patients
the benefits of pioneering treatment options in the core therapy areas of
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design and acquisition, the Mundipharma network of independent associated
companies delivers cutting-edge treatments to meet the most pressing needs of
healthcare professionals and patients. For further information please visit:
http://www.mundipharma.com

About Bendamustine

Bendamustine was first discovered in Germany 50 years ago in what was then the
German Democratic Republic (East Germany). In 2008 the US Food and Drug
Administration (FDA) approved bendamustine for the treatment of iNHL and
chronic lymphocytic leukemia (CLL), and it subsequently received European
approval in 2010 for certain types of iNHL, CLL and multiple myeloma.

Bendamustine has marketing authorisations in Germany, France, UK, Italy,
Spain, Austria, Switzerland, Sweden, Norway, Finland, Denmark, Poland,
Slovakia, Ireland, Cyprus, Iceland, Belgium, The Netherlands, Greece,
Slovenia, Portugal, Czech Republic, Romania and Bulgaria (Levact®,
Ribomustin®, Ribovact®) where it is marketed by the Mundipharma network of
independent associated companies.

Bendamustine is licensed (Levact®, Ribomustin®, Ribovact®) from Astellas
Deutschland GmbH.

In the United States, bendamustine (TREANDA®) is marketed by Teva
Pharmaceutical Industries Ltd. (NYSE: TEVA) and indicated for the treatment of
patients with CLL, and indolent B-cell NHL that progressed during or within
six months of treatment with rituximab or a rituximab-containing regimen.

SymBio Pharmaceuticals Ltd holds exclusive rights to develop and market
bendamustine HCL in Japan (sublicensed to Eisai Co Ltd) and selected Asian
countries including Hong Kong and Singapore. In South America and Australasia
the commercial rights are held by Janssen-Cilag Ltd.

CHOP-R/CVP-R Treatment Regimens

Rituximab plus chemotherapy, most commonly CHOP or CVP, is the current
first-line standard of care for patients with advanced iNHL, and mantle cell
lymphoma patients who are not fit for high dose chemotherapy. ^[12] CHOP, a
multi-drug chemotherapy regimen, is a combination of three chemotherapy
injections/infusions (cyclophosphamide, doxorubicin and vincristine) on a
single day, with a fourth agent (prednisone) taken orally for five days. Each
cycle is repeated every three weeks for 6-8 cycles. CVP treatment follows a
similar regimen but comprises two chemotherapy
injections/infusions(cyclophosphamide and vincristine), followed by a five-day
course of prednisone tablets.

References

1. Rummel MJ, Niederle N, Maschmeyer G, et al. Subanalysis of the StiL NHL
1-2003 Study: Achievement of Complete Response with Bendamustine-Rituximab
(B-R) and CHOP-R in the First-Line Treatment of Indolent and Mantle Cell
Lymphomas Results in Superior Survival Compared to Partial Response. Abstract
presented at ASH 2012. Available at
https://ash.confex.com/ash/2012/webprogram/Paper48063.html .

2. Flinn IW, Van der Jagt RH, Kahl BS, et al. An Open-Label, Randomized Study
of Bendamustine and Rituximab (BR) Compared with Rituximab, Cyclophosphamide,
Vincristine, and Prednisone (R-CVP) or Rituximab, Cyclophosphamide,
Doxorubicin, Vincristine, and Prednisone (R-CHOP) in First-Line Treatment of
Patients with Advanced Indolent Non-Hodgkin's Lymphoma (NHL) or Mantle Cell
Lymphoma (MCL): The Bright Study. Abstract presented at ASH 2012. Available at
https://ash.confex.com/ash/2012/webprogram/Paper51442.html .

3. Burke JM, Van der Jagt RH, Kahl BS, et al. Differences in Quality of Life
Between Bendamustine Plus Rituximab Compared with Standard First-Line
Treatments in Patients with Previously Untreated Advanced Indolent
Non-Hodgkin's Lymphoma or Mantle Cell Lymphoma. Abstract presented at ASH
2012. Available at https://ash.confex.com/ash/2012/webprogram/Paper49604.html
.

4. Ulrich Knauf W, Abenhardt W, Nusch A, Grugel R, Marschner N.
Bendamustine-Rituximab (BR) Replaces R-CHOP As "Standard of Care" in the
Treatment of Indolent Non-Hodgkin Lymphoma in German Hematology Outpatient
Centres. Abstract presented at ASH 2012. Available at
https://ash.confex.com/ash/2012/webprogram/Paper53051.html .

5. Rummel MJ, Lerchenmüller C, Greil R, et al. Bendamustin-Rituximab Induction
Followed by Observation or Rituximab Maintenance for Newly Diagnosed Patients
with Waldenström's Macroglobulinemia: Results From a Prospective, Randomized,
Multicenter Study (StiL NHL 7-2008 -MAINTAIN-; ClinicalTrials.gov Identifier:
NCT00877214). Abstract presented at ASH 2012.

6. Rummel MJ, Niederle N, Maschmeyer G, et al. Bendamustine plus rituximab
(B-R) versus CHOP plus rituximab (CHOP-R) as first-line treatment in patients
with indolent and mantle cell lymphomas (MCL): Updated results from the StiL
NHL1 study. J Clin Oncol 30, 2012 (suppl; abstr 3).

7. Cancer.Net Editorial Board. Lymphoma - Non-Hodgkin - Subtypes. Available at
http://www.cancer.net/cancer-types/lymphoma-non-hodgkin/subtypes . Accessed
November 2012.

8. Salles G, Seymour JF, Offner F, et al. Rituximab maintenance for 2 years in
patients with high tumour burden follicular lymphoma responding to rituximab
plus chemotherapy (PRIMA): a phase 3, randomised controlled trial. The Lancet,
1 January 2011: 9759;42 - 51.

9. Non-Hodgkin lymphoma incidence statistics: In the EU and worldwide. Cancer
Research UK. Available at
http://www.cancerresearchuk.org/cancer-info/cancerstats/types/nhl/incidence/#world
. Accessed November 2012. European Age-Standardised rates calculated by the
Cancer Research UK Statistical Information Team, 2011, using data from
GLOBOCAN 2008 v1.2, IARC, version 1.2 .

10. Gascoyne, Randy D. Hematopathology approaches to diagnosis and prognosis
of indolent B-cell lymphomas. ASH Education Program Book 2005.1 (2005):
299-306.

11. European Age-Standardised rates calculated by the Cancer Research UK
Statistical Information Team, 2011, using data from GLOBOCAN 2008 v1.2, IARC,
version 1.2 . Available at Non-Hodgkin lymphoma incidence statistics: In the
EU and worldwide. Cancer Research UK
http://www.cancerresearchuk.org/cancer-info/cancerstats/types/nhl/incidence/#world
. Accessed November 2012.

12. Gribben JG; How I treat indolent lymphoma. Blood 2007;109:4617-4626.

Contact: For further information please contact: Lara Dow,
Lara.Dow@mundipharma.co.uk, +44(0)7753-579842, Emma-Fleur Hartley,
Emma.Hartley@fleishmaneurope.com, +44(0)20-7395-7114
 
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