June 7th, 2011 Oxford, UK—Chroma Therapeutics Ltd. and Cell Therapeutics, Inc. (“CTI”) (NASDAQ: CTICD and MTA: CTIC) announced that interim results from the phase II OPAL study of tosedostat in elderly patients with relapsed or refractory acute myeloid leukemia (AML) were presented and discussed at the 2011 Annual Meeting of the American Society of Clinical Oncology (ASCO). Dr Farhad Ravandi of the University of Texas M.D. Anderson Cancer Center, who presented the poster during the ASCO discussion session, concluded that once daily oral tosedostat was well-tolerated and demonstrated encouraging response rates at the interim evaluation time point. This included a high response rate among patients who received prior hypomethylating agents, supporting further evaluation of tosedostat in this type of patient in both AML and MDS.
Tosedostat is a novel, orally administered AADR (amino acid deprivation response) inducer, which targets and deprives sensitive tumor cells of amino acids by blocking protein recycling resulting in tumor cell death.
“While only interim response evaluation data are available, the results are very encouraging especially when one considers the fragile and difficult to treat nature of the patient population studied,” said Dr Jorge Cortes, of the University of Texas M.D. Anderson Cancer Center, and lead investigator on the OPAL study.
“An interesting observation is that 9 of the 15 responders were observed in patients who failed prior hypomethylating agent therapy. These preliminary results support the preclinical data and suggest a rationale for exploring tosedostat in
the types of patient usually treated with hypomethylating agents like decitabine or azacytidine in both elderly AML and MDS (myelodysplastic syndrome).
“The interim data from OPAL are very encouraging and show a convincing effect in a population of patients with a very high unmet medical need who otherwise have a poor prognosis.” said Dr Martin Toal, Medical Director at Chroma Therapeutics. “The marked effect in patients with prior myelodysplastic syndromes or those who had failed prior therapy with hypomethylating agents was particularly noteworthy and points to the need for further investigation of tosedostat in both AML and MDS. The final data from the 6 month analysis of OPAL will be available soon and will answer additional important questions about whether there is a survival benefit associated with these positive responses.”
The phase II study enrolled 73 patients randomized to two tosedostat dose regimens—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 61% of the patients treated with Ara-C plus anthracycline or other Ara-C regimens, 33% of the patients treated with hypomethylating agents and 4% of the patients treated with other regimens. Fifty-two percent had been refractory to primary induction therapy and 21% had shown a response of less than six months. The overall response rate to tosedostat was 21% and was similar between treatment arms. In patients who were evaluable (i.e., had a post-baseline bone marrow assessment) (n=50) the response rate was 30%. Nine of the 15 responders (60%) had received prior hypomethylating agents suggesting that these patients were more likely to respond to tosedostat than those treated with traditional AML therapy. Tosedostat was generally well-tolerated. The most common grade = 3 treatment-related adverse events were febrile neutropenia (in 29% of patients) and thrombocytopenia (in 22% of patients).
The poster from the conference will be available at www.chromatherapeutics.com
Chroma Therapeutics Limited
Chief Executive Officer
+44 (0)1235 829120
Chief Financial Officer
+44 (0)20 7404 5959
Cell Therapeutics, Inc.
+1 206-272-4343 / +1 206-854-1200
Lindsey Jesch Logan
AML is a haematologic cancer that is an aggressive, fast-growing cancer that starts inside the bone marrow with the production of abnormal blood cells. The American Cancer Society estimated that 12,330 new cases of acute myeloid leukemia (AML) were diagnosed and approximately 8,950 deaths from AML occured in the U.S. in 2010. AML is generally a disease of older people, with the average patient age at onset of approximately 67 years. There remain a substantial proportion of elderly patients who do not receive intensive chemotherapy due to their inability to tolerate such regimens, and other risk factors. Therefore, there is a significant unmet medical need in developing a well-tolerated and effective treatment for these patients.
Tosedostat is an orally dosed aminopeptidase inhibitor which blocks the M1/17 family of aminopeptidases. Disrupting aminopeptidases deprives sensitive tumour cells of amino acids by blocking protein recycling, resulting in tumor cell death. Tosedostat has been studied in Phase I-II clinical trials both as a single agent and in combination with other chemotherapeutic agents. Such studies have demonstrated a significant anti-tumour response without the typical side effects of conventional, non-targeted cytotoxic therapies. Initial target indications include AML, MDS and multiple myeloma. CTI has exclusive marketing and co-development rights to Tosedostat in North, Central and South America.
About Chroma Therapeutics
Chroma Therapeutics, based in Oxford (UK), is a drug discovery and 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.
About Cell Therapeutics, Inc.
Headquartered in Seattle, CTI is a biopharmaceutical company committed to developing an integrated portfolio of oncology products aimed at making cancer more treatable. For additional information, please visit www.CellTherapeutics.com.