Orphan drug designation for pracinostat, volasertib and alvocidib in AML

摘要

The slow pace of progress in the therapeutic arena in acute myeloid leukemia (AML) [1 ] contrasts sharply with the rapid strides that have been made recently in unraveling the biology of the disease [2]. Somewhat surprising in the context of this difficult-to-treat disease is evidence that the average number of mutated genes per AML genome is relatively small [2]. The use of whole-genome or whole-exome sequencing and integrated genomic profiling strategies has led to recognition of the prognostic and predictive relevance of mutations in genes such as IDH1/2 and DNMT3A [3], which may potentially inform therapeutic choices, and possibly provide new therapeutic targets [4]. Despite these advances, only 40-45% of young adults and very few older patients are cured of their AML today [1]. Although small-molecule inhibitors of fms-like tyrosine kinase 3 (FLT3) have been under investigation for a decade, none is specifically approved for AML treatment [5], and while some of these (e.g., quizartinib) may serve as a "bridge" to allogeneic hematopoietic stem cell transplantation [5], acquired point mutations in the kinase domain of FLT3 have been described that confer substantial resistance to this agent [6].