On May 31, 2018 MEI Pharma, Inc. (Nasdaq: MEIP), a pharmaceutical company focused on leveraging its extensive development and oncology expertise to identify and advance new therapies for cancer, and Helsinn, a Swiss pharmaceutical group focused on building quality cancer care products, reported that a planned interim analysis in the ongoing Phase 2 study of pracinostat and azacitidine in higher risk MDS patients successfully met a predefined patient retention threshold (Press release, MEI Pharma, MAY 31, 2018, View Source [SID1234526997]). The positive outcome supports continuation of the study.
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Importantly, only 10% of patients discontinued from the study due to adverse events in the first 3 cycles of therapy. The 10% rate is consistent with the established discontinuation rate for azacitidine given as a monotherapy, and it meets the predefined threshold to continue enrollment in the study. Based on the positive interim analysis announced today, Helsinn and MEI are expanding open-label enrollment to a total of up to 60 MDS patients. The goal of this expanded cohort is to gain an estimate of the response rate and overall survival in this patient population to better inform the design of a global registration study.
"Patients with higher risk MDS currently face limited treatment options and poor outcomes," stated Ehab Atallah, M.D., Study Chair, Associate Professor of Medicine, Medical College of Wisconsin. "Given the substantial need among this patient group, I am very encouraged by my experience to date in this study investigating pracinostat in combination with azacitidine. Frequently, higher risk MDS develops into AML. The potential to offer patients a novel combination therapy that is generally well tolerated with the prospect for improved outcomes in MDS and possibly AML is exciting."
The ongoing Phase 2 open-label study is evaluating a 45 mg dose of pracinostat in higher risk MDS patients in order to improve tolerability and retain patients in study longer than in an earlier Phase 2 study evaluating a 60 mg dose. A prolonged treatment may result in a systemic exposure to pracinostat sufficient to achieve the desired treatment effect, unlike in the earlier study.
The Phase 2 Study
The ongoing Phase 2 dose optimization study is investigating a 45 mg dose of pracinostat in combination with the standard dose of azacitidine in patients with high and very high-risk MDS who are previously untreated with hypomethylating agents. 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 pre-planned interim analysis of the study established a 10% discontinuation rate among the first 20 evaluable patients treated, beating a predefined threshold in the first 3 treatment cycles. Having met this threshold, the study is expanding open-label enrollment to 60 patients. Patients will be followed for one year to evaluate safety and efficacy. If the expanded open-label study is successful, the companies intend to initiate a global registration study. To date 29 patients have completed at least one cycle of therapy.
The primary endpoints of the study are 1) safety and tolerability and 2) overall response rate, defined as complete remission (CR), partial remission (PR) and marrow CR. Secondary endpoints include CR rate, overall hematologic improvement (HI) response rate, clinical benefit rate (defined as rate of CR + PR + HI + Marrow CR), rate of cytogenetic complete response/remission, duration of response, rate of leukemic transformation, event-free survival, progression-free survival and overall survival.
The study as initially designed included two stages: the completed first stage that met the predefined discontinuation rate threshold, and a randomized and placebo-controlled second stage triggered upon meeting the predefined discontinuation threshold in the first stage. The study design is being amended by substituting stage 2 with an expanded open-label portion of the study to obtain data intended to better inform the design of a registration study upon successful completion of the Phase 2 study.
About Higher Risk MDS
Higher risk MDS (high and very high risk in the IPSS-R classification) is a serious medical condition, with median survival of less than 18 months. 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. Standard therapy with HMAs in higher risk MDS provides modest responses, though azacitidine has been shown to improve survival when compared to conventional care regimens. Patients who do not respond to HMAs or progress after therapy with HMAs have a very poor outcome, with a median survival of less than one year.
About Pracinostat
Pracinostat is an oral histone deacetylase ("HDAC") inhibitor that is in a pivotal Phase 3 study in combination with azacitidine for the treatment of adults with newly diagnosed acute myeloid leukemia ("AML") who are unfit for intensive chemotherapy. It is also being evaluated in a Phase 2 study in patients with high or very high-risk myelodysplastic syndrome ("MDS"). The U.S. Food and Drug Administration has granted Breakthrough Therapy Designation for pracinostat in combination with azacitidine for the treatment of patients with newly diagnosed AML who are ≥75 years of age or unfit for intensive chemotherapy.
In August 2016, Helsinn and MEI Pharma entered into an exclusive license, development and commercialization agreement for pracinostat in AML and other potential indications. The agreement provides that Helsinn is primarily responsible for development and commercialization costs for pracinostat in AML and other indications, including MDS. Pracinostat is an investigational agent and is not approved for commercial use in the U.S. and any country worldwide.