Data Show Encouraging Results for a Potential New Front-Line Treatment Approach in AML CAMBRIDGE, Mass., June 2
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
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
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
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 CantorCatherine Forte
(617) 768-6690 (617) 768-6881
SOURCE Genzyme Corp.
