Pracinostat is an orally available histone deacetylase (HDAC) inhibitor that is being developed for advanced hematologic diseases such as acute myeloid leukemia (AML) and myelofibrosis. HDACs 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.

Pracinostat has been tested in multiple Phase I and Phase II clinical trials in hematologic and solid tumor indications.
The results of these studies suggest that Pracinostat has potential best-in-class pharmacokinetic properties when compared to other oral HDAC inhibitors, with side effects often associated with drugs of this class, the most frequent of which are fatigue and myelosuppression.

In June 2013, we initiated a comprehensive development program for Pracinostat "in order to realize its full potential and determine the most efficient registration path forward." This development program included three Phase II clinical studies of Pracinostat in combination with azacitidine (marketed as Vidaza®) in front line MDS, refractory MDS and front line AML. Based on positive results from our AML study, we believe we have determined the most efficient registration path forward and intend to commit our resources toward further development of this combination in AML.

Acute Myeloid Leukemia

Pracinostat has demonstrated clinical evidence of single-agent activity in patients with AML. In a Phase I dose-escalation study, two out of 14 evaluable patients with AML (14%) achieved a complete remission (CR), with the responses enduring for more than 206 and 362 days, respectively. These results were presented at the American Society of Hematology (ASH) Annual Meeting in December 2010

In February 2014, the U.S. Food & Drug Administration (FDA) granted orphan drug designation to Pracinostat for the treatment of AML. The designation provides orphan status to drugs defined by the FDA as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases that affect fewer than 200,000 people in the U.S. Orphan designation qualifies us for certain development incentives, including tax credits for qualified clinical testing, prescription drug user fee exemptions and seven-year marketing exclusivity upon FDA approval. We also intend to seek orphan drug designation in the U.S. and Europe for Pracinostat in combination with azacitidine for the treatment of AML.

In November 2014, we completed enrollment in our open-label Phase II study of Pracinostat in combination with azacitidine in elderly patients with newly diagnosed AML. The study enrolled a total of 50 patients at 15 centers across the U.S. The median age in the study was 76 years. Patients received 60 mg of Pracinostat orally three times a week for three weeks followed by one week of rest and 75 mg/m2 of azacitidine via subcutaneous injection or intravenous infusion for the first seven days of each 28-day cycle. 

Results from the study were presented at the ASH Annual Meeting in December 2015. According to the oral presentation by principal investigator Dr. Guillermo Garcia-Manero, MD Anderson Cancer Center, 28 of the 50 patients in the study (56%) achieved the primary endpoint of CR plus complete response with incomplete blood count recovery (CRi) plus morphologic leukemia-free state (MLFS), including 21 patients (42%) who achieved a CR. Notably, 19 of the 21 patients who achieved a CR are still alive with a 100% one-year survival rate among all CR patients, indicating a correlation between CR and survival with this low intensity therapy.

Median overall survival for all 50 patients in the study has not been reached, with 28 patients still living and a median observation time of 14.3 months. These data compare favorably to a recent international Phase III study of azacitidine (AZA-001), which showed a median overall survival of 10.4 months with azacitidine alone and a CR rate of 19.5% in a similar patient population. Median survival among patients with high-risk cytogenetics in our study (n=21) was 13.3 months, more than double the median survival of the high-risk population in the AZA-001 study (6.4 months).

The combination of Pracinostat and azacitidine was generally well tolerated in the study, with no unexpected toxicities. The most common grade 3/4 treatment-emergent adverse events reported in >10% of all patients included febrile neutropenia, thrombocytopenia, anemia and fatigue.

Based on these findings, we are now preparing for a Phase III registration study of Pracinostat and azacitidine in elderly patients with newly diagnosed AML, which we plan to initiate in the second half of 2016. We look forward to sharing more information regarding the design of this study in the months ahead.


Pracinostat has shown evidence of activity when used in combination with a wide range of therapies in clinical and pre-clinical studies. Pre-clinical data published in the May 2012 issue of Blood Cancer Journal demonstrated synergistic activity when Pracinostat was combined with pacritinib, an experimental JAK2 inhibitor.

In a Phase II clinical trial in intermediate or high-risk myelofibrosis, 36% of patients (eight of 22) derived benefit from Pracinostat treatment, with 9% of patients (two of 22) having a clinical improvement (anemia response) and 27% (six of 22) experiencing some reduction in splenomegaly. These results were published in the September 2012 issue of Leukemia Research.

Pracinostat is currently being evaluated in a Phase II study in combination with ruxolitinib (marketed as Jakafi® and Jakavi®) in patients with myelofibrosis. The goal of this study is to learn if Pracinostat, when given in combination with ruxolitinib, can help to control myelofibrosis. The study, sponsored by the M.D. Anderson Cancer Center, began enrollment in early 2015.

Myelodysplastic Syndrome

Pracinostat has shown evidence of clinical activity when used in combination with azacitidine in patients with advanced myelodysplastic syndrome (MDS). Results from a pilot Phase II study presented at the ASH Annual Meeting in December 2012 showed an overall response rate of 89% (eight of nine). The combination of Pracinostat and azacitidine was generally well tolerated in the study; the most frequent side effects were nausea and fatigue.

In March 2015, we announced top-line data from a randomized, double-blind, placebo-controlled Phase II clinical study of Pracinostat in combination with azacitidine in intermediate-2 or high-risk patients with previously untreated MDS. The study enrolled 102 evaluable patients, randomized one-to-one, at 19 sites in the U.S. The top-line data showed the addition of Pracinostat to azacitidine did not increase the overall CR rate, the study's primary endpoint, compared to azacitidine alone. There were no new toxicities observed in the study. Fatigue, gastrointestinal toxicities and myelosuppresion occurred more frequently in the combination group and resulted in a higher rate of drug discontinuations compared to azacitidine alone, predominantly within the first two cycles of treatment.

Exploratory sensitivity analyses suggest that patients receiving Pracinostat plus azacitidine for more than four cycles appear to derive benefit compared to azacitidine alone, with hazard ratios for overall survival (0.59) and duration of response (0.48) both favoring the Pracinostat plus azacitidine arm. These data were presented at the ASH Annual Meeting in December 2015.

In December 2014, we reached the clinical response milestone in our open-label Phase II study of Pracinostat in hypomethylating agent (HMA)-refractory MDS. Of the first 28 patients who received Pracinostat in combination with azacitidine or decitibine (marketed as Dacogen®) after progressing while being treated with the same HMA alone, three achieved clinical responses -- one partial response (PR) and two marrow complete responses (mCR) -- exceeding the pre-specified clinical improvement rate for expansion of study enrollment. We completed enrollment with 39 patients in this arm and will continue to follow these patients for response and survival. A second arm, patients with stable disease following initial HMA therapy, was closed due to insufficient enrollment. There were no new or unexpected toxicities in the study. The most common treatment-emergent adverse events include anemia, fatigue and gastrointestinal disorders.

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