Study met primary endpoint of progression free survival with Campath
CAMBRIDGE, Mass. and Wayne, N.J., Dec. 11 /PRNewswire-FirstCall/ --
Genzyme Corporation (Nasdaq: GENZ) and Berlex Inc., a U.S. affiliate of
Schering AG, Germany (FSE: SCH), majority-owned by the Bayer Group, today
announced results from CAM307, an international Phase III clinical trial
comparing Campath(R) (alemtuzumab) with chlorambucil in previously
untreated patients with B-cell chronic lymphocytic leukemia (B-CLL). The
study data were presented at the 48th Annual Meeting of the American
Society of Hematology (ASH) in Orlando.
The study met its primary endpoint by demonstrating superior
progression free survival in patients treated with Campath versus
chlorambucil, with Campath reducing the risk of disease progression or
death by 42 percent (p=0.0001).
"Results from this study demonstrate that with up to twelve weeks of
Campath therapy, these patients achieved a median period of two years
before requiring additional treatment," stated lead investigator Peter
Hillmen, MB, ChB, of the Leeds General Infirmary, Leeds, United Kingdom.
"The high response rates, longer progression-free survival, and extended
treatment-free intervals in these patients, in addition to other clinical
data, support that Campath is one of the most active single agents in CLL
and confirm its place as a key component of any future studies in
combination or consolidation therapy."
Additional Study Results
As reported at ASH, and confirmed by an independent response review
panel, the secondary endpoint analyses showed that patients who received
Campath given for a median of nearly twelve weeks exhibited significantly
higher overall and complete response rates, with a manageable safety
profile, compared with those patients who were treated with chlorambucil
for a median of twenty-four weeks. The data showed a nearly 30 percent
greater (83% vs. 55%) overall response rate (ORR) among patients treated
with Campath vs. chlorambucil (p< 0.0001), and a 12-fold increase (24% vs.
2%) in complete response rates (CRR) in patients receiving Campath (p<
0.0001).
In addition, it was observed that 26 percent (9 out of 34) of complete
responders in the Campath arm achieved an MRD (minimal residual disease)
negative response as defined by testing below the level of B-CLL detection.
Of those MRD negative complete responders, all but one (8 out of 9) showed
no disease progression at a median follow-up of two years following
treatment.
"Based on these results, Campath has demonstrated significantly better
efficacy with a manageable safety profile against chlorambucil as
front-line therapy in B-CLL," stated Mark Enyedy, senior vice-president and
general manager of Genzyme's oncology business unit, who also noted that
this post- approval commitment study was completed within the time frame
agreed upon with the U.S. Food and Drug Administration (FDA). "We look
forward to working with the FDA regarding a supplement to the product
labeling to support treatment of patients earlier in the course of their
disease, and we believe these data offer the basis for incorporating
Campath into future front-line studies in consolidation and combination
therapy, and in high-risk patients," he added.
"We're encouraged that these data showed Campath to be a safe and
tolerable therapy, while providing a significant improvement in
progression- free survival," stated Richard Nieman, M.D., vice president
and head of medical affairs at Berlex. "This is good news for patients, who
are in need of more effective treatment options earlier in the course of
their disease."
About the study design, further results and safety
The international open-label, randomized trial with 297 enrolled
patients compared the efficacy and safety of Campath to chlorambucil, which
is considered by many to offer the most tolerable safety profile among
agents commonly used for previously untreated B-CLL patients. The study
examined a primary endpoint of progression free survival (PFS) and
secondary endpoints that included safety, response rate, response duration,
time to alternative treatment, and overall survival.
A correlation between the cytogenetic profile of the patients
participating in the CAM307 trial suggests a higher ORR and CRR in patients
with certain cytogenetic abnormalities. While the study was not powered to
assess differences in response to treatment based on cytogenetics, results
on small numbers of patients appear encouraging. In patients with a 17p
deletion, a marker of poor prognosis, ORR was three times higher and PFS
almost five times higher among patients receiving Campath versus those
receiving chlorambucil (ORR 64% vs. 20% and PFS 10.7 months versus 2.2
months respectively); however, due to the small number of patients in this
group (11 patients in the Campath arm and 10 patients in the chlorambucil
arm), this trend did not reach statistical significance.
Overall, the tolerability profile for Campath was predictable and
manageable. Although rates of grade 3-4 neutropenia, leukopenia and
lymphopenia were higher in the Campath arm, there were no significant
differences reported in febrile neutropenia, or in grade 3-4
thrombocytopenia and anemia. Only 16 percent of patients developed CMV
reactivation associated with clinical signs or symptoms, all of which were
managed with antiviral therapy. There was no treatment related mortality in
the Campath arm, whereas one treatment-related death occurred in the
chlorambucil arm.
For Campath, the most common drug-related events, excluding CMV-related
adverse events and occurring in at least 10 percent of patients, were
pyrexia, chills, nausea, urticaria, hypotension and rash, whereas for
chlorambucil, they were nausea and vomiting.
Excluding adverse events associated with CMV reactivation, the only
treatment-related grade 3-4 adverse event in the Campath arm occurring in
more than five percent of patients was pyrexia. In the results of this
trial, serious adverse events related to treatment occurred in 27 percent
of Campath patients and seven percent of patients on chlorambucil.
Hospitalization for CMV reactivation in some countries contributed to the
difference in SAE frequency between the two treatment arms in this trial.
The trial randomized 297 previously untreated patients at 44 medical
centers in the United States and Europe. Patients were treated with either
30 mg of Campath intravenously three times per week for a maximum of 12
weeks, inclusive of dose escalation periods, or 40 mg/mē of chlorambucil
per oral administration once every 28 days to a maximum of 12 cycles.
About Chronic Lymphocytic Leukemia
CLL is the most prevalent form of adult leukemia, affecting
approximately 120,000 people in Europe and the United States. The disease
is most commonly diagnosed among people age 50 or older. CLL is
characterized by the accumulation of functionally immature white blood
cells (lymphocytes) in the bone marrow, blood, lymph tissue, and other
organs. Two types of lymphocytes are present in the blood, B cells and T
cells. About 95 percent of CLL cases involve cancerous B cells. Because
these B cells have a longer than normal life span, they begin to build up
and "crowd out" the normal, healthy blood cells. The accumulation of
functionally immature cells in the bone marrow excludes the generation of
healthy cells and can become fatal. Symptoms include fatigue, bone pain,
night sweats, fevers, and decreased appetite and weight loss. Bone marrow
infiltration leads to a lack of healthy blood cells, thus leading to
fatigue, susceptibility to bleedings and weakening of the immune system,
exposing the patient to a higher risk of infection.
About Campath
Campath received accelerated approval in 2001 and CAM307 was the
primary post-approval commitment study designed to support full approval.
Campath is currently indicated for the treatment of B-CLL in patients who
have been treated with alkylating agents and who have failed fludarabine
therapy. Determination of the effectiveness of Campath is based on overall
response rates. Comparative, randomized trials demonstrating increased
survival or clinical benefit such as improvement in disease-related
symptoms have not yet been conducted.
Campath works by targeting the "CD52" antigen, which is one of the most
common antigens found on B and T cells. When Campath binds to this CD52
antigen, it activates the immune system to destroy targeted cells not only
in the blood but also in the bone marrow. Campath is not currently
indicated as a first-line treatment in CLL.
Campath should be administered under the supervision of a physician
experienced in the use of antineoplastic therapy. Campath has a boxed
warning which includes events of hematologic toxicity, infusion reactions,
and infections/opportunistic infections.
Campath is contraindicated in patients who have active systemic
infections, underlying immunodeficiency (e.g., seropositive for HIV), or
known Type 1 hypersensitivity or anaphylactic reactions to Campath or to
any one of its components.
The most commonly reported infusion-related adverse events were rigors,
drug-related fever, nausea, vomiting, and hypotension. Hematologic
toxicities included pancytopenia/marrow hypoplasia, anemia,
thrombocytopenia, neutropenia, and profound lymphopenia, and should be
monitored. Infections reported included sepsis, pneumonia, and
opportunistic infections such as CMV, candidiasis, aspergillosis, and
mucormycosis.
Genzyme and Berlex's parent company are co-developing Campath in
oncology and other indications.
About Genzyme
One of the world's leading biotechnology companies, Genzyme is
dedicated to making a major positive impact on the lives of people with
serious diseases. This year marks the 25th anniversary of Genzyme's
founding. Since 1981, the company has grown from a small start-up to a
diversified enterprise with more than 8,500 employees in locations spanning
the globe and 2005 revenues of $2.7 billion. Genzyme has been selected by
FORTUNE as one of the "100 Best Companies to Work for" in the United
States.
With many established products and services helping patients in more
than 80 countries, Genzyme is a leader in the effort to develop and apply
the most advanced technologies in the life sciences. The company's products
and services are focused on rare inherited disorders, kidney disease,
orthopaedics, cancer, transplant and immune diseases, and diagnostic
testing. Genzyme's commitment to innovation continues today with a
substantial development program focused on these fields, as well as heart
disease and other areas of unmet medical need.
About Berlex
Berlex, a U.S. affiliate of Schering AG, Germany (FSE: SCH), is
committed to addressing unmet medical needs through research and
development in the areas of oncology, gastroenterology, women's health,
diagnostics and neurology. Berlex also markets diagnostic imaging agents,
innovative treatments in the areas of female health care and oncology, as
well as specialized therapeutics for life-threatening and disabling
diseases of the central nervous system and cardiovascular system. Berlex
has business operations in New Jersey, California and Washington. For more
information, please visit http://www.berlex.com.
Berlex Oncology is building a prominent leadership position through
research and development of a range of hematological and solid tumor
treatments, and is strongly invested in bringing to market an innovative
and broad oncology R&D portfolio of systemic and targeted therapies,
potentially offering novel therapeutic options for people with cancer.
This press release contains forward-looking statements, including
statements about the results of the CAM307 trial, and regulatory plans and
expected timelines for the expansion of the product label for Campath into
earlier-line CLL. These statements are subject to risks and uncertainties
that could cause actual results to differ materially from those projected
in these forward-looking statements. These risks and uncertainties include,
among others: that final results of the CAM307 trial demonstrate safety and
efficacy comparable to the preliminary data that have been released to
date, the actual timing and content of submissions to and decisions made by
the U.S. Food and Drug Administration and other regulatory authorities, and
the other risks and uncertainties described in reports filed by Genzyme
with the Securities and Exchange Commission. Please see the disclosure
under the heading "Factors Affecting Future Operating Results" in the
Management's Discussion and Analysis of Financial Condition and Results of
Operations section of Genzyme's Quarterly Report on Form 10-Q for the third
quarter ended September 30, 2006 for a more complete discussion of these
and other risks. Genzyme cautions investors not to place substantial
reliance on the forward-looking statements contained in this press release.
These statements speak only as of the date of this press release, and
Genzyme undertakes no obligation to update or revise the statements.
Certain statements in this press release that are neither reported
financial results nor other historical information are forward-looking
statements, including but not limited to, statements that are predictions
of or indicate future events, trends, plans or objectives. Undue reliance
should not be placed on such statements because, by their nature, they are
subject to known and unknown risks and uncertainties and can be affected by
other factors that could cause actual results and Berlex's plans and
objectives to differ materially from those expressed or implied in the
forward-looking statements. Berlex, Inc. undertakes no obligation to update
publicly or revise any of these forward-looking statements, whether to
reflect new information or future events or circumstances or otherwise.
Genzyme(R) and Campath(R) are registered trademarks of Genzyme
Corporation. All rights reserved.
Genzyme's press releases and other company information are available at
http://www.genzyme.com and by calling Genzyme's investor information line
at 1-800-905-4369 within the United States or 1-703-797-1866 outside the
United States.
Berlex press releases and other company information are available at
http://www.berlex.com and by calling 1-888-BERLEX-4 or 1-888-237-5394.
Genzyme Contacts: Berlex Contacts:
Maria Cantor (media) Kimberly Wix (media)
(617) 768-6690 (973) 305-5258
Carol Miceli (investors) Joanne Marion (investors)
(617) 768-6602 (973) 487-2164
SOURCE Genzyme Corporation
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Related links:
http://www.genzyme.com/
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CONTACT:
Maria Cantor (media), +1-617-768-6690, or
Carol Miceli (investors), +1-617- 768-6602, both of Genzyme
Corporation; or Kimberly Wix (media), +1-973-305-5258, or Joanne
Marion (investors), +1-973-487-2164, both of Berlex
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