MEI Pharma, Inc., an oncology company focused on the clinical development of novel therapies for cancer, has dosed its first patient in a phase II clinical trial of its lead drug candidate Pracinostat in combination with Vidaza (azacitidine) in patients with previously untreated intermediate-2 or high-risk myelodysplastic syndrome (MDS). The randomized, double-blind trial is designed to evaluate the safety and efficacy of Pracinostat compared to placebo when combined with Vidaza, a drug approved by the US Food & Drug Administration (FDA) for the treatment of MDS.
Results from an earlier pilot study of Pracinostat in combination with Vidaza in patients with intermediate-2 or high-risk MDS were presented at the American Society of Haematology (ASH) Annual Meeting in December 2012 showed an overall response rate of 89 per cent (eight out of nine), including seven patients who achieved either a complete remission (CR) or a complete remission with incomplete blood count recovery (CRi).
“The initiation of this randomized phase II trial is an important milestone in the clinical development of Pracinostat,” said Robert D Mass, MD, chief medical officer of MEIPharma. “The results from the pilot study reported at ASH were very exciting and helped to inform the design of this more robust, placebo-controlled trial. Now, our goal is to build on these preliminary data and get a more precise estimate of the clinical benefit of Pracinostat in combination with standard-of-care.”
The multi-centre phase II trial is expected to enroll 100 patients with a one-to-one randomization. Completion of enrollment is anticipated by June 2014 with topline data in December 2014. The primary endpoint of the study is complete remission (CR). Secondary endpoints include overall response rate (CR+CRi+PR), haematologic improvement, duration of response, progression-free survival, rate of leukaemic transformation, overall survival and safety. The trial is being conducted in collaboration with the Sarah Cannon Research Institute; Dr Guillermo Garcia-Manero of the MD Anderson Cancer Centre is the principal investigator.
“This represents the first in a series of phase II studies we have planned for Pracinostat in the months ahead,” said Daniel P Gold, Ph.D., president and chief executive officer of MEI Pharma. “We believe that Pracinostat truly has the potential to become a best-in-class drug. We intend to execute a comprehensive development programme in order to realize its full potential and determine the most efficient registration path forward.”
In addition to the randomized phase II clinical trial in frontline MDS, the Company is also preparing for the initiation of two open-label phase II trials of Pracinostat: one in combination with Vidaza in frontline acute myeloid leukaemia (AML) in the fall of 2013 and the other in combination with Vidaza or Dacogen (decitabine) in patients with refractory MDS soon thereafter.
Pracinostat is an orally available histone deacetylase (HDAC) inhibitor that has been tested in a number of phase I and exploratory phase II clinical trials in advanced haematologic disorders and solid tumour indications in both adult and paediatric patients. Pracinostat has been generally well tolerated in more than 200 patients to date, with readily manageable side effects that are often associated with drugs of this class, such as fatigue. Pracinostat has exhibited pharmacokinetic properties that compare favorably to other oral HDAC inhibitors, including Zolinza (vorinostat), which is approved by the FDA for the treatment of cutaneous T-cell lymphoma. In addition to the evidence of clinical activity observed in combination with Vidaza in patients with MDS, Pracinostat has demonstrated single-agent activity in AML, including two CRs out of 14 patients (14 per cent) in a dose-escalation trial, with durable responses persisting up to 362 days.
MEIPharma owns exclusive worldwide rights to Pracinostat.