MERCK, VERTEX REPORT DATA ON AURORA KINASE INHIBITOR

Merck and Vertex Pharmaceuticals have announced results of a Phase I clinical trial for MK-0457 (also known as VX-680), an investigational small-molecule inhibitor of Aurora, FLT-3, JAK-2 and BCR-ABL kinases. The study showed that MK-0457 demonstrated clinical activity in select patients with chronic myelogenous leukemia (CML), Philadelphia-chromosome-positive acute lymphocytic leukemia (Ph+ ALL) with the T315I BCR- ABL mutation and also in patients with refractory JAK-2 positive myeloproliferative disorders (MPD). The results were presented in an oral presentation at the annual meeting of the American Society of Hematology.

The Phase I, dose-escalation clinical trial evaluated 44 adult patients with advanced leukemias and MPDs who were treated with MK-0457 given as a five-day intravenous infusion every two-to-three weeks. Out of the 15 patients with refractory CML, nine patients had a T315I BCR-ABL mutation. Eight of these nine T315I patients had either a hematologic and/or cytogenetic response to MK-0457 following multiple cycles of treatment. The six of 15 patients without the T315I BCR-ABL mutation did not exhibit any clinical responses.

In addition, two patients in the study with Ph+ ALL carrying the T315I mutation had either hematologic and/or cytogenetic responses, including one patient who had a clinical response with a full molecular remission. Six of nine patients with myeloproliferative disorders having the V617F activating mutation in JAK-2 also had clinical responses. These clinical responses were consistent with drug effects observed in leukemic cells.

In the study, no drug-related non-hematological toxicities have been observed with MK-0457, and therefore a maximum-tolerated dose has not yet been established.