LUGANO, Switzerland and San Diego—Helsinn Group and MEI Pharma have released interim data from a Phase 2 study evaluating pracinostat, a histone deacetylase inhibitor, in combination with azacitadine for the treatment of patients with IPSS-R high/very high-risk of Myelodysplastic Syndrome (MDS). The data demonstrate a 9% discontinuation rate due to adverse events, a substantially lower rate than observed in an earlier study, as well as an encouraging 36% complete response rate among patients receiving at least 6 cycles of treatment. These data were presented yesterday at the 2018 American Society of Hematology (ASH) Annual Meeting.
Ehab Atallah, MD, Study Chair, Associate Professor of Medicine at the Medical College of Wisconsin said, “Treatment options for patients with a higher risk of MDS are still limited and following diagnosis the survival rate is less than 18 months with the current standard of care. At the time of the Phase 2 data announced this year in May, I was excited to see that this treatment demonstrated that it can be offered to patients as a combination therapy and potentially improve outcomes. We’re pleased that the threshold for expansion of this study has been met, and I look forward to continuing to observe the progress of this combination treatment.”
Higher risk MDS has a median survival of less than 18 months. The high and very high-risk groups represent the highest unmet need in MDS, with median survival estimates of only 1.6 years and 0.8 years, respectively. The only curative therapy is allogeneic stem cell transplantation (SCT); however most patients with MDS are not candidates for SCT, given their typically advanced age, comorbidities and lack of a suitable donor.
The ongoing Phase 2 open-label study is evaluating a 45 mg dose of pracinostat in combination with azacitadine in order to improve safety/tolerability and retain patients in study longer than in an earlier Phase 2 study evaluating a 60 mg dose. Prolonged treatment is envisaged to result in a systemic exposure to pracinostat sufficient to achieve the desired treatment effect. The data reinforce results from a planned May 2018 interim analysis meeting a predefined discontinuation threshold and suggest a reduced dose of pracinostat may allow MDS patients to remain on treatment longer, and increase the likelihood of a treatment response.
Treatment in the current Phase 2 study was generally well-tolerated: adverse events ≥ Grade 3 reported in 20% or more of patients are febrile neutropenia, anemia, neutropenia and thrombocytopenia. If the current Phase 2 open-label study is successful, Helsinn intends to initiate a global registration study.
The primary endpoints of the study are safety and tolerability and overall response rate, defined as complete remission (CR), partial remission (PR) and marrow CR. Secondary endpoints include CR rate, overall hematologic improvement, progression-free survival and overall survival, among others.
“The interim data demonstrating a 9% discontinuation rate due to adverse events, a substantially lower rate than observed in the earlier study, as well as an encouraging complete response rate to date of 36% of patients reaching the first disease assessment at 6 months, represents an opportunity to advance a promising new treatment for patients with high/very high-risk disease that currently have limited options,” added Richard Ghalie, MD, Senior Vice President, Clinical Development at MEI Pharma.
As of the end of October 2018, 55 patients have completed at least one cycle of therapy. The data demonstrate a 9% discontinuation rate due to adverse events, 4% of which were early discontinuations (within the first 3 treatment cycles). 15% of patients discontinued because they advanced to SCT. The discontinuation rate reported continues to meet the pre-defined threshold from the planned interim analysis conducted in May 2018 and is consistent with the discontinuation rate for azacitadine administered as a single agent. In the group of patients receiving at least 6 cycles of treatment, the complete response rate is 36%. The median duration on therapy is 4.7 months (range 0.5-13 months).
“Helsinn bolsters its commitment in developing pracinostat in combination with hypomethylating agents in patients with AML and with high risk MDS,” mentioned Ruben Giorgino, MD, PhD, Helsinn Group Head of Clinical Development. “Moving forward to the second stage of this really important Phase 2 clinical trial in MDS patients represents an important next step in our efforts to understand the potential benefit of pracinostat in these patients with poor prognosis and modest response to hypomethylating monotherapy.”