Date: 2017-06-05
Type of
information: Presentation of results at a congress
phase: 2
Announcement: presentation of results at the American Society of Clinical Oncology (ASCO) annual meeting, in Chicago
Company: Mei Pharma (USA - CA) Helsinn Group (Switzerland)
Product: pracinostat
Action
mechanism:
- histone deacetylase inhibitor. Pracinostat is an oral histone deacetylase (HDAC) inhibitor that has been tested in a number of Phase I and Phase II clinical trials in advanced hematologic disorders and solid tumor indications in both adult and pediatric patients. Since August 2016, MEI Pharma has entered into an exclusive licensing, development and commercialization agreement with Helsinn for pracinostat for the treatment of acute myeloid leukemia and other potential indications.
Disease: acute myeloid leukemia
Therapeutic
area: Cancer - Oncology
Country: USA
Trial
details: The open-label Phase 2 study enrolled a total of 50 patients at 15 centers across the U.S. Median age in the study was 75 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. The combination of pracinostat and azacitidine had no unexpected toxicities. The most common grade 3/4 treatment-emergent adverse events reported in >10% of all patients included thrombocytopenia, febrile neutropenia, neutropenia, fatigue and anemia.
Latest
news:
- • On June 5, 2017, Helsinn and MEI Pharma announced findings from a genetic mutation analysis of patients in a Phase II clinical study of pracinostat and azacitidine in acute myeloid leukemia, including a significant correlation between genetic mutations in the DNA methylation pathway and clinical response. These data are being presented at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.
- Available samples from 41 of the 50 patients enrolled in the Phase II study were sequenced to characterize the genetic mutation profile of these patients. The overall mutation profile of the patients in this study appear to be generally typical of an older population with AML and are also common in myelodysplastic syndrome (MDS). The most frequent mutations, occurring in 37% of samples studied (15/41), were found in the DNA methylation pathway, including DNMT3A, IDH1, IDH2 and TET2. Patients with these mutations had a complete response (CR) rate of 60%, a significant improvement (p=0.027) over patients with the wild-type genes (22%).
- Notably, the phase II analysis also showed that median overall survival was roughly equivalent in patients with mutations typically associated with de novo AML (18.1 months) and secondary AML (17.7 months). In a recent study, the standard-of-care regimen of cytarabine and daunorubicin (7+3) in patients with secondary AML showed a median overall survival of 5.95 months.
- Results from the Phase II study of pracinostat and azacitidine in elderly patients with AML showed a median overall survival of 19.1 (95%CI: 10.0-26.5) months, one-year survival of 62% and a CR rate of 42%. CR rate and overall survival were consistent across patient subsets. Responses were durable (median CR+CRi 17.2 months), blast clearance was rapid (median 8 weeks) and maximum clinical benefit required prolonged therapy (> 6 months) in some patients. The combination of pracinostat and azacitidine had no unexpected toxicities. The most common grade 3/4 treatment-emergent adverse events reported in >10% of all patients included thrombocytopenia, febrile neutropenia, neutropenia, fatigue and anemia. These results were presented at the American Society of Hematology (ASH) Annual Meeting in December 2016 (see below).
- • On December 5, 2016, Helsinn and MEI Pharma announced final results from a Phase 2 clinical study of pracinostat and azacitidine in elderly patients with acute myeloid leukemia who were not eligible for induction chemotherapy, including evidence of prolongation of survival in the overall population and across a number of patient subgroups. In an oral presentation at the American Society of Hematology (ASH) Annual Meeting, Dr. Guillermo Garcia-Manero, MD Anderson Cancer Center, principal investigator of the study, reported a median overall survival of 19.1 (95%CI: 10.7-26.5) months, one-year survival of 62% and a complete response (CR) rate of 42%.
- Site recruitment is now ongoing for the global Phase 3 study of pracinostat and azacitidine in newly diagnosed AML patients who are ?75 years of age or unfit for intensive induction chemotherapy.
- • On December 7, 2015, MEI Pharma announced positive results from a Phase II study of pracinostat in combination with azacitidine (marketed as Vidaza®) in elderly patients with newly diagnosed acute myeloid leukemia (AML). The results were presented at the American Society of Hematology (ASH) Annual Meeting in Orlando. 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 complete response plus complete response with incomplete blood count recovery plus morphologic leukemia-free state, 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)1, 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 this 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, MEI Pharma will now begin to prepare for a Phase III registration study of pracinostat and azacitidine in elderly patients with newly diagnosed AML. The company plans to initiate this study in the second half of 2016.
- • On November 6, 2014, MEI Pharma announced that data from a Phase II clinical study of pracinostat in combination with azacitidine (marketed as Vidaza®) in elderly patients with newly diagnosed acute myeloid leukemia has been accepted for presentation at the upcoming American Society of Hematology (ASH) Annual Meeting in San Francisco. The presentation is entitled "Pracinostat in Combination with Azacitidine Produces a High Rate and Rapid Onset of Disease Remission in Patients with Previously Untreated Acute Myeloid Leukemia (AML). As reported in the abstract (as of August 1, 2014), eight of the 14 patients evaluable for efficacy achieved a complete response (CR) or a complete response with incomplete blood count recovery (CRi). The authors conclude that this CR CRi rate of 57% is high compared to historical results with hypomethylating agents alone in this population, noting that the responses occur rapidly, most within the first two cycles. No responders have progressed to date. The combination of pracinostat and azacitidine has been generally well-tolerated in the study, with no unexpected toxicities. The most common treatment emergent adverse events were neutropenia neutropenic fever, thrombocytopenia, nausea, fatigue and anemia.
- In June 2014, the Company reported a CR CRi rate of 33% in the first nine patients enrolled, meeting the pre-specified CR/CRi rate required to advance to the second stage of the study. The open-label study is enrolling a total of 40 patients to further define the tolerability and efficacy of the regimen, including remission duration.
Is
general: Yes
