MEI Pharma recently presented promising clinical results from a new oral phosphatidylinositol 3 kinase (PI3K) delta inhibitor, ME-401, that may improve the therapeutic window in cancer patients compared to other PI3K delta inhibitors.
The data was presented at the American Association for Cancer Research (AACR) Annual Meeting in New Orleans, in a poster titled “Clinical Pharmacokinetics and Pharmacodynamics of ME-401, an Oral, Potent, and Selective Inhibitor of Phosphatidylinositol 3-Kinase P110δ, Following Single Ascending Administration to Healthy Volunteers.”
PI3K delta has been shown to have a critical role in the survival and proliferation of certain hematological cancers. “PI3K delta is a class of drugs that has shown great promise in the treatment of B-cell malignancies, but with certain toxicities,” Daniel P. Gold, PhD, president and chief executive officer of MEI Pharma, said in a press release. “We believe this provides an opportunity for a next-generation drug that can produce therapeutic responses at a safe, effective dose.”
ME-401 is a potent and selective inhibitor of PI3K delta with a distinct chemical structure from other PI3K delta inhibitors, including the approved drug idelalisib (available as Zydelig). In December 2012, data presented at the American Society of Hematology Annual Meeting revealed higher pre-clinical activity for ME-401 compared to idelalisib. Researchers now provided data suggesting that ME-401 also has an excellent pharmacokinetic and pharmacodynamic profile, with a half-life that allows once-daily administration, which will improve the therapeutic window of PI3K delta inhibitors.
MEI Pharma researchers presented data from a Phase I study, where the safety and tolerability of ME-401 was addressed in healthy volunteers. In total, 15 volunteers were given single ascending doses of 10, 30, 60, 90, and 150 mg to select the optimal dose for further clinical evaluation. Data revealed that ME-401 was generally well-tolerated at all dose levels, with only one subject experiencing drug-related mild headache and pain after a 60 mg dose.
The company wants to start a Phase Ib dose-escalation study in June 2016 to address ME-401 efficacy in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) or follicular non-Hodgkin’s lymphoma (fNHL). MEI Pharma expects to enroll between 42 and 84 patients in the study, with a starting dose of 60 mg. “Now the goal of our upcoming Phase Ib study will be to show a large therapeutic window in cancer patients. We expect to dose the first patient in this study by the end of June and look forward to providing an update later this year,” said Dr. Gold.