High & very high risk
Pracinostat is an oral histone deacetylase (HDAC) inhibitor being evaluated in a Phase 2 study in patients with high or very high-risk myelodysplastic syndrome (MDS).
In August 2016, Helsinn Group and MEI Pharma entered into an exclusive license, development and commercialization agreement for pracinostat. The agreement provides that Helsinn is primarily responsible for development and commercialization costs for pracinostat. Pracinostat is an investigational agent and is not approved for commercial use in the U.S. and any country worldwide.
MECHANISM OF ACTION
HDAC inhibitors belong to a larger set of proteins collectively known as epigenetic regulators that can alter gene expression by chemically modifying DNA or its associated chromosomal proteins. Abnormal activity of these regulators is believed to play an important role in cancer and other diseases.
Myelodysplastic Syndrome is a type of blood cancer in which the bone marrow does not make enough healthy blood. MDS is normally a disease of the elderly and sometimes may progress into AML, which is a more rapidly growing cancer.
MDS CLINICAL PROGRAM
Pracinostat is being investigated in an open-label, Phase 2 dose optimization study evaluating 64 patients with high and very high-risk MDS who are previously untreated with hypomethylating agents. The Phase 2 open-label study is evaluating a 45mg dose of pracinostat in combination with the standard dose of azacitidine. Data from the Phase 2 study (n=64) presented as part of the American Society of Clinical Oncology 2020 Virtual Scientific Program in June 2020 demonstrated an estimated median overall survival (OS) rate of 23.5 months with a 1-year OS rate of 77%. The median follow-up was 17.6 months (range, 15.7–18.8) and the overall response rate (ORR) was 33% (21/64), all of which are complete responses (CR). The clinical benefit rate (CR, mCR plus hematologic improvement [HI], mCR with no HI, or HI with no mCR) was 77% (49/64). Twenty seven percent of patients (17/64) proceeded to a stem cell transplant while on study. Eleven percent of patients discontinued treatment because of adverse events. The most common grade ≥3 treatment emergent adverse events were hematologic, and included decreased neutrophil count (50%), anemia (39%), febrile neutropenia (34%), decreased platelet count (33%), thrombocytopenia (27%), and decreased white blood cell count (20%).