On 14th August 2017, the U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation to H3B-8800 for the treatment of patients with Acute Myeloid Leukemia (AML).1
High frequencies of somatic mutations in core spliceosome genes, including Splicing Factor 3b Subunit 1 (SF3B1) U2 Small Nuclear Ribonucleoprotein Auxiliary Factor 1 (U2AF1) and Serine/Arginine-Rich Splicing Factor 2 (SRSF2), have been reported in AML patients. Mutations in splicesome genes result in aberrant mRNA splicing and have been shown to contribute to leukemogenesis in AML patients. H3B-8800 is an oral, potent and selective inhibitor of SF3B1. H3B-8800 binds and blocks the activity of SF3B1 thereby modulating RNA splicing, which in turn leads to an induction of apoptosis and prevention of cell proliferation. 2,3
H3B-800 is currently being investigated in a phase I study (NCT02841540) which aims to evaluate the safety, pharmacokinetics and pharmacodynamics of H3B-800 in patients with AML.