Data Show Encouraging Results for a Potential New Front-Line Treatment
Approach in AML
CAMBRIDGE, Mass., June 2 /PRNewswire-FirstCall/ -- Genzyme Corp.
(Nasdaq: GENZ) reported preliminary data today from a fully-enrolled
pivotal, phase 2 study examining the safety and effectiveness of Clolar(R)
(clofarabine) as a single agent in previously untreated, older adult
patients with acute myelogenous leukemia (AML) who are unlikely to benefit
from conventional "7+3" anthracycline plus cytarabine-based induction
chemotherapy.
Results from the CLASSIC-II clinical trial show that patients with
unfavorable prognostic factors who received single agent clofarabine
exhibited a 45 percent overall remission rate based on investigator
assessment, with manageable treatment-related side effects. Importantly,
the 30 day all-cause mortality, one of the secondary endpoints in this
study, was only 9.6 percent, which compares favorably to existing treatment
options. Data from the study were presented at the annual meeting of the
American Society of Clinical Oncology (ASCO) in Chicago.
"The therapeutic outcomes for older AML patients have not improved in
the past thirty years," stated Mark J. Enyedy, president of Genzyme
Oncology, a business unit of Genzyme Corporation. "These data highlight the
potential of clofarabine to become an innovative and much needed treatment
option for these patients. We look forward to submitting a supplemental new
drug application in the United States later this year to expand the current
product label into front-line therapy for adult AML and to make a similar
filing in Europe around this same time."
Study Results
As reported at ASCO, investigator-assessed response data show a 45
percent overall remission rate among patients treated with single agent
clofarabine, with 40 percent of patients achieving a complete remission to
therapy and 5 percent attaining a complete remission with incomplete
platelet recovery. Overall remission in this study is defined as a patient
achieving either complete remission or complete remission with incomplete
platelet recovery. Secondary endpoints include duration of remission,
disease free survival, overall survival, safety and thirty-day mortality.
The CLASSIC II study data are based on clinical responses from 115 patients
at 20 sites in the U.S.
Data also show overall remission rates of 50 percent among patients
with prior blood disorders; 43 percent in patients with adverse
cytogenetics; 40 percent in patients 70 years of age and older; and 38
percent in patients with an ECOG performance status of 2. Remission rates
in patients with up to three pre-defined risk factors required for study
enrollment also exceeded 40 percent.
The study also demonstrated that the toxicity profile of clofarabine
was predictable and manageable. Drug-related adverse events occurring in
more than 15 percent of patients included nausea, febrile neutropenia,
vomiting, diarrhea and rash; most were grade 1 or 2. As expected, Grade 4
neutropenia and thrombocytopenia occurred in a majority of patients. Only
five of 115 patients discontinued treatment due to an adverse event or
toxicity precluding further therapy. The study has completed enrollment and
patients are being followed for remission duration, disease-free survival
and overall survival. An independent panel of hematologists and
hematopathologists are confirming the investigators' assessment of
responses.
"In addition to the excellent overall safety and efficacy findings we
are observing with single agent clofarabine, we also see impressive
responses in older patients with poor prognostic cytogenetic abnormalities
when treated with the drug," stated Harry P. Erba, MD, Ph.D., University of
Michigan, one of the co-principal investigators for this study. "This study
helps to define a new approach to treatment for patients unlikely to
benefit from conventional 7+3 induction chemotherapy and provides support
for the importance of assessing cytogenetics prior to induction treatment."
"The positive results seen in this study provide a compelling case for
a novel, effective, therapeutic option for older adult patients with AML
who have multiple unfavorable prognostic factors," added Hagop Kantarjian,
M.D. MD Anderson Cancer Center and the other co-principal investigator for
the CLASSIC II study. "In our published research from MD Anderson, older
AML patients with one to three unfavorable prognostic factors are at risk
of lower complete remission rates and higher 60-day mortality. We look
forward to analyzing the final independently-assessed study results,
particularly the remission duration data, for this very difficult-to-treat
population."
In addition to presentation at ASCO, a podium appearance of the
preliminary CLASSIC-II data also will be delivered by Dr. Erba at the
upcoming European Hematology Association meeting in Copenhagen, Denmark on
Sunday, June 15.
Study Design
Patients in the CLASSIC-II study must have previously untreated AML, be
60 years or older and be unlikely to benefit from conventional induction
chemotherapy based on the presence of at least one of the following adverse
prognostic factors: age greater than or equal to 70, pre-existing
hematological disorder such as myelodysplastic syndrome (MDS), poor health
performance, or intermediate or unfavorable cytogenetics. Patients also had
to be previously untreated and unlikely to benefit from conventional
induction chemotherapy (7+3 anthracycline plus cytarabine) based on the
presence of at least one of these poor prognostic factors at baseline.
Patients received an induction cycle of intravenous clofarabine
administered as 30mg/m2 per day for five consecutive days then, based on
their response, received up to five additional cycles of treatment at a
dose of 20 mg/m2 per day for five consecutive days.
Significant Unmet Medical Need
The CLASSIC II study is designed to address a high unmet medical need
among older AML patients who currently have limited treatment options.
According to the American Cancer Society, each year approximately 6,500
people over the age of 60 are diagnosed with AML in the U.S. The median
survival for those receiving therapy can vary from one to thirteen months,
and the five-year survival rate over the past three decades remains at less
than 10 to 15 percent. Older AML patients often have disease features such
as unfavorable (adverse) cytogenetics and pre-existing blood disorders such
as MDS that result in lower response rates and worse treatment outcomes to
conventional induction chemotherapy compared with younger patients. In
addition, conventional induction chemotherapy is poorly tolerated in older
patients with unfavorable risk factors, and early induction mortality
usually ranges from 10-30 percent but can exceed 30 percent in older
patients with a poor performance status.
This study builds on promising results from two prior studies of single
agent clofarabine in previously untreated older patients with AML deemed
unfit for chemotherapy, based mostly on poor performance status and
presence of co-morbid illnesses. These studies were conducted by Alan
Burnett, M.D., of Cardiff University in the United Kingdom and presented at
earlier American Society of Hematology meetings.
Clolar Clinical Development
A separate, phase 3 pivotal study (CLASSIC I) of clofarabine in
relapsed adult AML patients aged 55 and older and previously treated with
at least one, but not more than two, prior induction regimens is underway.
This randomized, double-blind, placebo-controlled study will compare the
combination of clofarabine and cytarabine (Ara-C) to cytarabine alone.
A second phase 3 study of clofarabine sponsored by the Eastern
Cooperative Oncology Group is expected to begin enrolling patients next
year. This study will compare single agent clofarabine to conventional
induction chemotherapy in untreated AML patients age 60 and older who are
considered suitable for conventional induction chemotherapy.
Clolar is indicated for the treatment of pediatric patients 1 to 21
years old with relapsed or refractory ALL after at least two prior
regimens. This use is based on the induction of complete responses.
Randomized trials demonstrating increased survival or other clinical
benefit have not been conducted.
Genzyme also is actively exploring additional therapeutic indications
for Clolar, including in MDS.
Genzyme Hosts Investor Call Tomorrow Morning
Genzyme will host an investor call tomorrow morning, Tuesday, June 3 at
10 a.m. EST. The preliminary data from the CLASSIC-II pivotal study will be
reviewed and there will be opportunity for investors to ask questions of
Genzyme.
To participate in the call, please dial 1-888-982-7287 in the U.S. or
1-210-234-0251 outside of the U.S. The participant passcode is "Genzyme."
A replay of this call will be available by dialing 1-800-695-3397. This
call will also be available live on the investor events section of
http://www.genzyme.com. Replays of the call will be available until 10:59 p.m. on
June 10, 2008.
About Clolar
Clolar has Orphan Drug designation for adult and pediatric ALL, and
seven years of market exclusivity in the United States for
relapsed/refractory pediatric ALL. The FDA also granted six months of
extended market exclusivity to Clolar under the Best Pharmaceuticals for
Children Act.
Clolar should be administered under the supervision of a qualified
physician experienced in the use of antineoplastic therapy. Suppression of
bone marrow function, which is usually reversible and dose dependent,
should be anticipated and is likely to increase the risk of infection,
including severe sepsis. Administration of Clolar results in a rapid
reduction of peripheral leukemia cells. Patients should be evaluated and
monitored for signs and symptoms of tumor lysis syndrome and cytokine
release (e.g., tachypnea, tachycardia, hypotension, pulmonary edema) that
could develop into systemic inflammatory response syndrome (SIRS)/capillary
leak syndrome, and organ dysfunction. Clolar should be discontinued
immediately in the event of clinically significant signs or symptoms of
SIRS or capillary leak syndrome.
The most common side effects seen after Clolar treatment, regardless of
causality, were gastrointestinal tract symptoms, including vomiting,
nausea, and diarrhea; hematologic effects including anemia, leukopenia,
thrombocytopenia, neutropenia, and febrile neutropenia; and infection.
Liver and kidney function should be assessed prior to and during
treatment with Clolar, as the liver is a target organ for Clolar toxicity
and Clolar is excreted primarily through the kidneys. Concomitant use of
medications known to induce hepatic toxicity should be avoided. Cardiac
disorders, including tachycardia, pericardial effusion, and left
ventricular systolic dysfunction, have been noted in up to 35% of pediatric
patients treated with Clolar. However, the presence of these disorders in
patients prior to Clolar administration and/or previous therapy or
concurrent illness in patients receiving Clolar makes the etiology of these
disorders unclear.
Clolar may cause fetal harm when administered to a pregnant woman.
Women of childbearing potential should be advised to avoid becoming
pregnant and avoid breast feeding while receiving treatment with Clolar.
For more information about Clolar, please call 1-800-RX CLOLAR or visit
http://www.CLOLAR.com.
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. Since 1981, the company has grown from a small start-up
to a diversified enterprise with more than 10,000 employees in locations
spanning the globe and 2007 revenues of $3.8 billion. In 2007, Genzyme was
chosen to receive the National Medal of Technology, the highest honor
awarded by the President of the United States for technological innovation.
With many established products and services helping patients in nearly
90 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 diagnostic testing. Genzyme's
commitment to innovation continues today with a substantial development
program focused on these fields, as well as immune disease, cardiovascular
disease, and other areas of unmet medical need.
This press release contains forward-looking statements, including
statements regarding the potential administration, dosing and therapeutic
benefit of Clolar in various cancer indications; the expected results of
the data generated from the Clolar clinical trials; and the requirements
and plans for regulatory filings and approvals for Clolar in additional
indications. These risks and uncertainties include, among others, the
timing of discussions with the FDA regarding clinical studies and approval
of Clolar in additional indications; the timing and content of decisions by
the FDA related to clinical trials and approval of Clolar in additional
indications; the actual efficacy and safety of Clolar for the indications
in which it is being tested; and the risks and uncertainties described in
reports filed by Genzyme with the U.S. Securities and Exchange Commission,
including without limitation the factors discussed under the caption "Risk
Factors" in Genzyme's Quarterly Report on Form 10-Q for the quarter ended
March 31, 2008. We caution investors not to place undue reliance on the
forward-looking statements contained in this press release. These
statements speak only as of the date of this press release, and we
undertake no obligation to update or revise the statements.
Genzyme(R) and Clolar(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 1-678-999-4572 outside the
United States.
Media Contact: Investor Contact:
Maria Cantor Catherine Forte
(617) 768-6690 (617) 768-6881
SOURCE Genzyme Corp.
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Related links:
http://www.CLOLAR.com
http://www.genzyme.com/
http://www.prnewswire.com/comp/104284.html/
CONTACT:
Media, Maria Cantor, +1-617-768-6690, or
Investor, Catherine Forte, +1-617-768-6881, both of Genzyme Corp.
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