A top cancer researcher from MD Anderson recently reported positive clinical trial data from cancer treatment pharmaceutical developer Array BioPharma Inc.’s ARRY 614 at the 2013 Annual Meeting of the American Society of Hematology. Guillermo Garcia-Manero, M.D., Professor, Department of Leukemia, Division of Cancer Medicine, at The University of Texas MD Anderson Cancer Center in Houston, reported that the experimental drug showed positive efficacy in patients with myelodysplastic syndromes (MDS) during recent clinical trials for the drug.
“The emerging results from this study with ARRY-614 are very promising,” said Dr. Garcia-Manero in recent comments. “ARRY-614 was generally well tolerated in these lower-risk MDS patients and I am particularly encouraged with the platelet effects observed in patients with thrombocytopenia, including platelet transfusion independence. Responses were seen in patients for whom hypomethylating agents had failed, a group with no available treatment options.”
ARRY-614 is currently being studied in ongoing dose-escalation clinical trials involving patients with low/intermediate-1 risk MDS, which features a population of more than 100,000 patients in developed countries. According to an Array press release, “In a previous study, using a different formulation of ARRY-614, multi-lineage activity was observed with the most promising effects seen in patients with thrombocytopenia and neutropenia, with several platelet transfusion-dependent patients becoming transfusion-independent. Array is evaluating an enhanced formulation of ARRY-614 in the current dose-escalation clinical trial. Pharmacokinetic and pharmacodynamics assays performed as part of the trial have demonstrated improved bioavailability and target coverage relative to the previously evaluated formulation. Mature data from this trial is expected in 2014. With these results, Array intends to discuss future development plans with regulatory authorities.”
They key behind ARRY-614 is that it acts as a potent inhibitor of p38/Tie2, with a mechanism of action that is different from other MDS treatments currently on the market. To date, the dose-escalation portion of the clinical trial established the maximum tolerated dose, and subsequent expansion cohorts have been fully enrolled.
According to the company and its recent findings in their ongoing clinical trials, “of patients currently evaluable for efficacy, 21 percent achieved a Hematologic Improvement, as defined byInternational Working Group 2006 (IWG). Of particular interest, 44 percent of platelet-transfusion dependent patients achieved Transfusion Reduction, and 31 percent achieved Transfusion Independence. Lower risk MDS patients with severe low platelet counts have a particularly poor prognosis. The most common treatment-related adverse events across all doses were rash (39 percent), nausea (17 percent), and atrial fibrillation (13 percent). The majority of these events were mild or moderate in severity.”
Michael Needle, M.D., Chief Medical Officer, Array BioPharma, noted that, “Significant unmet needs remain in the treatment of MDS,” adding, “ARRY- 614 is thought to operate at the progenitor cell level, distinct from currently available therapies, offering a unique mechanism of action for treatment of the cytopenias associated with MDS.”