Initial data from a Phase III comparative study suggest efficacy and safety
with Campath(R), even in poor-prognosis patients
CAMBRIDGE, Mass. and WAYNE, N.J., June 3 /PRNewswire-FirstCall/ --
Genzyme Corporation (Nasdaq: GENZ) and Berlex Oncology, a business unit of
Berlex Laboratories, a U.S. affiliate of Schering AG, Germany (FSE: SCH;
NYSE: SHR), today announced interim results from CAM307, an international
confirmatory Phase III clinical trial comparing Campath(R) (alemtuzumab)
with chlorambucil in previously untreated patients with progressive B-cell
chronic lymphocytic leukemia (B-CLL). Preliminary results of the secondary
endpoint from this study showed that patients who received the monoclonal
antibody Campath exhibited significantly higher overall and complete
response rates, with a manageable safety profile, compared with those
patients who were treated with chlorambucil. The data were presented at the
42nd Annual Meeting of the American Society of Clinical Oncology (ASCO) in
Atlanta.
Study Results
The open-label, randomized trial with 297 patients compared the
efficacy and safety of Campath to chlorambucil, which is considered by many
to offer the most tolerable safety profile for previously untreated
patients. The study examined a primary endpoint of progression free
survival and secondary endpoints that included safety, response rate and
overall survival.
As reported at ASCO, a pre-specified independent interim review of the
secondary endpoint data showed a nearly 30 percent greater (83% vs. 56%)
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 therapy (p< 0.0001).
In the comparison of safety parameters of Campath vs. chlorambucil, the
rates of grade 3-4 thrombocytopenia, anemia, and serious infections, other
than CMV, were found to be comparable between treatment arms. Although the
rates of CMV, neutropenia and leukopenia were higher in the Campath arm,
the difference in the incidence of febrile neutropenia was found to be
insignificant.
A correlation between the cytogenetic profile of the patients
participating in the CAM307 trial suggest a statistically significant ORR
and CRR were observed in patients with certain cytogenetic abnormalities.
Statistically significant higher response rates to Campath were observed in
patients with a 13q deletion, a common genetic event observed in patients
with B-CLL, and in the ORR of patients with 11q deletions, a cytogenetic
abnormality typically associated with poor prognosis. In patients with a
17p deletion, another marker of poor prognosis, ORR was 3 times higher
among patients receiving Campath vs. those receiving chlorambucil, 64% vs.
20% respectively; however, due to the small number of patients in this
group (10 patients in the Campath arm and 11 patients in the chlorambucil
arm), this trend did not reach statistical significance.
Lead investigator Peter Hillmen, MB, ChB, of the Leeds General
Infirmary, Leeds, United Kingdom, stated, "In addition to the excellent
overall safety and efficacy findings we are observing thus far in CAM307,
we also saw impressive responses in patients with poor prognostic
cytogenetic abnormalities when treated with Campath. This group of poor
risk patients have very low response rates and a short survival when
treated with conventional chemotherapy. The good results seen with Campath
promise a novel, more effective therapeutic option for these patients with
poor risk CLL. We therefore look forward to receiving the final study
results of Campath in relation to responses and survival in these
difficult-to-treat populations."
Campath received accelerated approval in 2001 and 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. Genzyme and Berlex's parent company, which holds
exclusive worldwide marketing and distribution rights to Campath, are
co-developing Campath in oncology and other indications. The product is
marketed in the U.S. by Berlex Laboratories.
The results presented at ASCO represent interim safety and efficacy
data to be released from CAM307, a comparative, confirmatory trial being
conducted to satisfy post-approval commitments to U.S. and European health
authorities (FDA and EMEA). Once the final data from the study's primary
endpoint of progression-free survival are available, Genzyme and Berlex
expect to file an application seeking to expand the product's current label
to include previously untreated B-CLL patients who require therapy.
"Based on these preliminary results, Campath may have significantly
better efficacy with manageable safety against chlorambucil as front-line
therapy in B-CLL," stated Mark Enyedy, senior vice-president and general
manager of Genzyme's oncology business unit. "We look forward to advancing
Campath further in its clinical development and to working with the FDA
regarding a supplement to the product label to treat patients earlier in
the course of their disease. We are also very pleased to have conducted
this post-approval commitment study in the timeframe we committed to the
FDA."
"These impressive interim results from the CAM307 study are very
encouraging for our ongoing efforts to bring new treatment options to
patients with CLL, and particularly to those with high-risk disease,"
stated Richard Nieman, M.D., Vice President and Head of Medical Affairs at
Berlex.
Safety Results and Study Design
Interim efficacy and safety data suggest that previously untreated
B-CLL patients who received Campath as a single agent have an excellent
response rate with a manageable toxicity profile. As expected, the most
common drug administration-related events noted to date were pyrexia,
rigors, nausea, hypotension, and vomiting. Overall, nausea and vomiting
were more frequent in the chlorambucil arm. In the interim results of this
trial, serious adverse events related to treatment occurred in 25 percent
of Campath patients and 6 percent of patients on chlorambucil.
The difference in SAE frequency observed may be explained by CMV
viremia/infection that was treated in hospitals in some countries,
therefore classified as grade 3-4 SAEs, and which all seem to have been
managed successfully. The incidence of grade 3-4 thrombocytopenia and
anemia appear to be comparable in both treatment arms. Grade 3-4
neutropenia and leukopenia as well as serious infections (due largely to
the incidence of CMV infections) appear to be more frequent in the Campath
arm. However, the difference in the incidence of febrile neutropenia was
found to be insignificant. One likely treatment-related death occurred in
the chlorambucil arm.
The trial randomized 297 previously untreated patients with progressive
disease requiring treatment at 44 medical centers in Europe and the United
States. Patients were treated with either 30 mg of Campath IV three times
per week for a maximum of 12 weeks, inclusive of dose escalation periods,
or 40 mg/m2 of chlorambucil PO 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
involvement also leads to weakening of the immune system, exposing the
patient to a higher risk of infection.
About Campath
Campath is the first and only humanized monoclonal antibody approved
for the treatment of B-CLL in patients who have failed both alkylating
agents and fludarabine phosphate treatment. 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.
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 8,000 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; NYSE: SHR),
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.
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.
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
quarter ended March 31, 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.
Genzyme(R), Campath(R), and MabCampath(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) Kimberley Jordan (media)
(617) 768-6690 (973) 305-5340
Kristen Galfetti (investors) Joanne Marion (investors)
(617) 768-6563 (973) 487-2164
SOURCE Genzyme Corporation; Berlex Oncology
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Related links:
http://www.genzyme.com
http://www.berlex.com/
http://www.prnewswire.com/comp/104284.html/
CONTACT:
Maria Cantor (media), +1-617-768-6690,
Kristen Galfetti (investors), +1-617- 768-6563, both of Genzyme;
or Kimberley Jordan (media), +1-973-305-5340, or Joanne Marion
(investors), +1-973-487-2164, both of Berlex
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