| Preclinical | Phase I | Phase II | Phase III | Marketed | |
| Tosedostat |
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AML is one of the most common types of leukemia in adults. Acute myeloid leukemia (AML), also known as acute myelogenous leukemia, is a cancer of the myeloid line of blood cells, 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 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. These symptoms include fatigue, shortness of breath, easy bruising and bleeding, and increased risk of infection. Several risk factors and chromosomal abnormalities have been identified, but the specific cause is not clear. As an acute leukemia, AML progresses rapidly and is typically fatal within weeks or months if left untreated.
AML has several subtypes; treatment and prognosis varies among subtypes. Five-year survival varies from 15–70%, and relapse rate varies from 33-78%, depending on subtype. AML is treated initially with chemotherapy aimed at inducing a remission; patients may go on to receive additional chemotherapy or a hematopoietic stem cell transplant. Recent research into the genetics of AML has resulted in the availability of tests that can predict which drug or drugs may work best for a particular patient, as well as how long that patient is likely to survive.
Tosedostat (formerly CHR-2797) is a novel, orally administered, once-daily dosed aminopeptidase inhibitor that induces an amino acid deprivation response (AADR), which is selectively toxic to blast cells from acute myeloid leukemia and certain other types of cancer cells. Tosedostat has anti-tumor activity in a number of preclinical tumor models, both as a single agent and in synergy with cytotoxic agents such as carboplatin, cytarabine and paclitaxel, and demethylating agents which are standard therapies for myelodysplasia. Phase I-II studies have shown tosedostat is well-tolerated and has promising clinical efficacy in AML.
Tosedostat is the only small molecule aminopeptidase inhibitor under clinical development.
CTI has development and marketing rights to tosedostat in the Americas under a March 2011 collaboration agreement with Chroma Therapeutics, Ltd (Oxford, UK).