Spliceosome

The FDA grants H3B-8800 Orphan Drug Designation for the treatment of AML

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.

References
  1. BuisnessWire: H3 Biomedicine Granted Orphan Drug Designation of H3B-8800 for Treatment of Acute Myelogenous Leukemia and Chronic Myelomonocytic Leukemia. 2017 August 14. http://www.businesswire.com/news/home/20170814005226/en/H3-Biomedicine-Granted-Orphan-Drug-Designation-H3B-8800   [Accessed 2017 Aug 14].
  2. Steensma D.P. et al. H3B-8800-G0001-101: A first in human phase I study of a splicing modulator in patients with advanced myeloid malignancies. J Clin Oncol 35, no. 15 (suppl; TPS7075). 2017 American Society of Clinical Oncology (ASCO) Annual Meeting, 2017 June 2–6; Chicago, IL, USA.
  3. NCI Drug Dictionary: splicing inhibitor H3B-8800. https://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=784315 [Accessed 2017 Aug 14].