Oxford, 4 March 2013 – Chroma Therapeutics Limited announced today that
The Lancet Oncology has published the results of the OPAL Study, a Phase 2
study of two dosing regimens of tosedostat in elderly patients with relapsed or
refractory acute myeloid leukaemia (AML). Tosedostat is a novel, oral
aminopeptidase inhibitor which deprives tumour cells of the amino acid building
blocks they need to make proteins necessary for tumour cell survival. The lead
investigator for the study 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, Texas.
The study addressed the unmet medical need in older patients who have failed to
adequately respond to conventional first line treatment and in whom further
treatment options are limited by toxicity concerns. Twenty-two percent of patients
had responses to tosedostat of partial remission or better and a further 29% had
stable disease. The most marked effects appeared to occur in patients who had
previously suffered with myelodysplastic syndrome (MDS) or those that had
received previous treatment for AML with hypomethylating agents (HMA).
Adverse events were generally mild, predictable and manageable.
About the OPAL Study
This Phase 2 multicenter, randomised study evaluated the safety and efficacy of
two dose regimens of tosedostat to determine an appropriate regimen for future
clinical studies. The study treated 73 patients randomised between 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 for AML had been Ara-C plus
anthracycline or other Ara-C regimens for 58% of patients, HMAs for 36% and
other regimens for 7%. Fifty-two percent of patients had not obtained a complete
remission from primary induction. As previously presented at the 53rd American
Society of Hematology Annual Meeting, other results included:
? 10% (7/73) achieving a complete remission (CR) or CRp and a further 12%
(9/73) achieving a partial remission or morphological leukaemia free state.
? High response rates were observed in patients who previously received
HMAs or initially were diagnosed with MDS, with 38% (10/26) and 37%
(7/19), respectively, achieving partial remission (PR) or better.
? Median overall survival (OS) for patients achieving <5% blasts (CR, CRp,
MLFS) was 322 days; PR 195 days; and SD 162 days.
? Adverse 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 serious adverse event was febrile neutropenia reported in
29% of patients.
“There are limited therapeutic options available for elderly patients who, after
failing hypomethylating agents, 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.”
Dr Martin Toal, Chief Medical Officer at Chroma, commented: “The results of
OPAL maintain the promise seen in earlier studies with tosedostat. Along with
the data from ongoing combination studies, this study provides an excellent basis
for designing a Phase 3 programme for a new therapeutic approach for older
patients who require a tolerable but effective treatment option”.
The publication by Dr. Cortes, et al. titled "Results of a Phase 2 study of two
dosing regimens in elderly patients with relapsed or refractory acute myeloid
leukemia - The OPAL Study,” is available at http://www.thelancet.com/journals/
Chroma Therapeutics Limited
Richard Bungay Chief Executive Officer +44 (0)1235 829120
Jon Coles +44 (0)20 7404 5959
About Chroma Therapeutics
Chroma Therapeutics, 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.
Tosedostat is an orally dosed aminopeptidase inhibitor which deprives sensitive
tumour cells of amino acids by blocking protein recycling, resulting in tumour cell
death. Tosedostat has been studied in Phase 1 and Phase 2 clinical trials both
as a single agent and in combination with other chemotherapeutic agents. Such
studies have demonstrated significant anti-tumour response without the typical
side effects of conventional, non-targeted cytotoxic therapies. Tosedostat is
licensed by Chroma from Vernalis plc and is sub-licensed to Cell Therapeutics,
Inc. in the Americas.