Tosedostat OPAL Study in Acute Myeloid Leukemia Published in Lancet Oncology
SEATTLE, March 4, 2013
SEATTLE, March 4, 2013 /PRNewswire/ --Cell Therapeutics, Inc.(CTI) (NASDAQ
and MTA: CTIC) and Chroma Therapeutics Ltd. announced today that Lancet
Oncology has published results from the OPAL Phase 2 study of tosedostat in
elderly patients with relapsed or refractory acute myeloid leukemia (AML).
Tosedostat is an oral aminopeptidase inhibitor which has been shown to deprive
tumor cells of the amino acid building blocks they need to make proteins
necessary for tumor cell survival. The lead author was Dr. Jorge Cortes,
Professor of Medicine and Internist, Department of Leukemia, Division of
Cancer Medicine, The University of Texas MD Anderson Cancer Center in Houston,
The trial showed that once-daily oral tosedostat resulted in a disease control
rate of 51%. Subset analyses suggested the greatest benefit occurred in the
difficult-to-treat patients with prior myelodysplastic syndrome (MDS) or those
that had received prior hypomethylating therapy (HMA). Adverse events were
mild, predictable and manageable.
About the OPAL Study
This Phase 2 multicenter, randomized study evaluated the safety and efficacy
of two dose regimens of tosedostat to determine an appropriate regimen for
future clinical studies. The study enrolled 73 patients randomized to two
treatment arms: tosedostat 120 mg once daily for six months or 240 mg once
daily for two months followed by 120 mg once daily for four months. The median
age of the patients was 72 years old. Prior primary induction therapy for AML
included 58% of the patients treated with Ara-C plus anthracycline or other
Ara-C regimens, 36% of the patients treated with HMAs and 7% of the patients
treated with other regimens. Fifty-two percent had been refractory to primary
induction therapy. As previously presented at the 53^rd American Society of
Hematology Annual Meeting, results included:
oOverall response rate (ORR) of 22% (16/73), with 10% (7/73) achieving a
complete response (CR) and 29% (21/73) of patients achieving stable
disease (SD) for a disease control rate of 51%.
oHigh response rates were observed in patients who previously received HMAs
or initially were diagnosed with MDS, with an ORR of 38% (10/26) and 37%
oMedian overall survival (OS) for patients achieving a CR was 322 days;
partial response (PR) 195 days; and SD 162 days.
oAdverse events were similar between dosing groups. Tosedostat was
generally well-tolerated, with the majority of adverse events of grade 1
and 2. The most common treatment-related serious adverse event was febrile
neutropenia reported in 29% of patients.
"There are limited therapeutic options available for elderly patients who,
after failing hypomethylating therapy, experience AML progression from MDS,"
said Dr. Cortes. "The novel mechanism of action and observed response rate in
this completed Phase 2 study suggests that tosedostat could address this unmet
medical need. We are currently conducting a Phase 2 study investigating the
combination of tosedostat with azacytidine - an HMA, or low-dose cytarabine, a
standard leukemia therapy in patients with relapsed or refractory AML and MDS
- to determine if tosedostat would be safe and more effective when used in
combination with these agents."
The publication by Dr. Cortes, et al. titled "Two dosing regimens of
tosedostat in elderly patients with relapsed or refractory acute myeloid
leukemia (OPAL): a randomized open-label phase 2 study," is available at
About Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS)
About 13,780 new cases of AML were expected to be diagnosed in the United
States in 2012.^1 As of January 2008 an estimated 30,993 people were living
with (or were in remission from) AML. Although AML can occur at any age,
adults aged 60 years and older are more likely to develop the disease than
younger people.^2 AML is a cancer characterized by the rapid growth of
abnormal white blood cells that accumulate in the bone marrow and interfere
with the production of normal blood cells. AML may develop from the
progression of other diseases such as myelodysplastic syndrome (MDS), a blood
cancer that also affects the bone marrow leading to a decrease in circulating
red blood cells. AML is the most common acute leukemia affecting adults, and
its incidence increases with age. The symptoms of AML are caused by
replacement of normal bone marrow with leukemic cells, which causes a drop in
red blood cells, platelets, and normal white blood cells leading to infections
and bleeding. AML progresses rapidly and is typically fatal within weeks or
months if left untreated. Although a substantial proportion of younger
individuals who develop AML can be cured, AML in the elderly typically
responds poorly to standard therapy with few complete remissions.
Tosedostat is an oral, aminopeptidase inhibitor that has demonstrated
significant anti-tumor responses in blood-related cancers and solid tumors in
Phase 1-2 clinical trials. CTI has exclusive marketing and co-development
rights toChroma Therapeutics Ltd.'s drug candidate tosedostat in North,
Central andSouth America.
Cell Therapeutics, Inc. (NASDAQ and MTA: CTIC) is a biopharmaceutical company
committed to the development and commercialization of an integrated portfolio
of oncology products aimed at making cancer more treatable. CTI is
headquartered in Seattle, WA. For additional information and to sign up for
email alerts and get RSS feeds, please visit www.CellTherapeutics.com.
About Chroma Therapeutics
Chroma Therapeutics Limited, based in Oxford (UK), is a drug development
company focused in the fields of oncology and inflammatory disorders. Chroma
is building a broad pipeline of first- or best-in-class treatments utilising
its expertise in chromatin biology and its novel intracellular accumulation
technologies, which include the ability to selectively target drugs to
macrophages. Chroma is backed by a number of leading specialist investors,
including Abingworth, Essex Woodlands, Gilde, Phase4 and The Wellcome Trust.
More information about Chroma can be found at www.chromatherapeutics.com.
1. American Cancer Society, Cancer Facts & Figures 2012. Available at
http://tinyurl.com/8kylgc7. Accessed February 2013.
2. The Leukemia and Lymphoma Society, Acute Myeloid Leukemia, Rev. 2011.
Available at http://tinyurl.com/d72ycja. Accessed February 2013.
This press release includes forward-looking statements that involve a number
of risks and uncertainties, the outcome of which could materially and/or
adversely affect actual future results and the trading price of CTI's
securities. Specifically, the risks and uncertainties that could affect the
development of tosedostat include risks associated with preclinical and
clinical developments in the biopharmaceutical industry in general and with
tosedostat in particular including, without limitation, the potential failure
of tosedostat to prove safe and effective for the treatment of AML, MDS,
multiple myeloma, blood related cancers and solid tumors as determined by the
U.S. Food and Drug Administration and/or the European Medicines Agency; that
tosedostat may not be more effective when used in combination with
azacytidine; that CTI cannot predict or guarantee the pace or geography of
enrollment of its clinical trials; determinations by regulatory, patent, and
administrative governmental authorities; competitive factors; technological
developments; costs of developing and producing tosedostat; and the risk
factors listed or described from time to time in CTI's filings with
theSecurities and Exchange Commission, including, without limitation, CTI's
most recent filings on Forms 10-K, 10-Q and 8-K. Except as may be required by
law, CTI does not intend to update or alter its forward-looking statements
whether as a result of new information, future events, or otherwise.
Contacts at CTI:
Contact at Chroma Therapeutics:
+44 (0)1235 829137
SOURCE Cell Therapeutics, Inc.
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