Quizartinib — a Phase 2B trial treatment for acute myeloid leukemia

 

quizartinib

Ambit Biosciences

 13 MAY 2013

Ambit Biosciences (NASDAQ:AMBI) is a biotech company that focuses on treatments that inhibit kinases, which are drivers for diseases such as cancer. Three drugs are in development, with the lead one being quizartinib — a Phase 2B trial treatment for acute myeloid leukemia.

However, AMBI’s collaboration agreement with Astellas Pharma (OTC:ALPMY) is set to expire in September, and if it is not replaced, it could mean a delay in Phase 3 trials for quizartinib. Keep in mind that AMBI generated $23.8 million in collaboration revenues last year.

 

Quizartinib (AC220) is a small molecule receptor tyrosine kinase inhibitor that is currently under development for the treatment of acute myeloid leukaemia. Its molecular target isFLT3, also known as CD135 which is a proto-oncogene.^[1]

Flt3 mutations are among the most common mutations in acute myeloid leukaemia due tointernal tandem duplication of Flt3. The presence of this mutation is a marker of adverse outcome.

Specifically, Quizartinib selectively inhibits class III receptor tyrosine kinases, including FMS-related tyrosine kinase 3 (FLT3/STK1), colony-stimulating factor 1 receptor (CSF1R/FMS), stem cell factor receptor (SCFR/KIT), and platelet derived growth factor receptors (PDGFRs).Mutations cause constitutive action of Flt3 leading to resulting in inhibition of ligand-independent leukemic cell proliferation and apoptosis

It had good results in a phase II clinical trial for refractory AML – particularly in patients who went on to have a stem cell transplant.^[2]

 

1.  Chao, Qi; Sprankle, Kelly G.; Grotzfeld, Robert M.; Lai, Andiliy G.; Carter, Todd A.; Velasco, Anne Marie; Gunawardane, Ruwanthi N.; Cramer, Merryl D.; Gardner, Michael F.; James, Joyce; Zarrinkar, Patrick P.; Patel, Hitesh K.; Bhagwat, Shripad S. (2009). “Identification of N-(5-tert-Butyl-isoxazol-3-yl)-N’-{4-[7-(2-morpholin-4-yl-ethoxy)imidazo[2,1-b][1,3]benzothiazol-2-yl]phenyl}urea Dihydrochloride (AC220), a Uniquely Potent, Selective, and Efficacious FMS-Like Tyrosine Kinase-3 (FLT3) Inhibitor”. Journal of Medicinal Chemistry 52 (23): 7808–7816.
2.  Drug Tames Refractory AML. ASH Dec 2012