Vertex Pharmaceuticals Inc.'s collaboration with Merck & Co. Inc. to develop Aurora kinase inhibitors in cancer encountered a bump in the road after preliminary safety data indicated a potential cardiovascular effect in one patient treated with lead candidate, MK-0457 (VX-680).
Safety findings from that subject indicated QTc prolongation, a condition that often precedes cardiac arrest, and "as a precaution," said Vertex spokesman Ian McConnell, "recruitment was suspended" in an ongoing Phase II trial of MK-0457 in chronic myelogenous leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL) patients with a T3151 bcr-abl mutation and an ongoing Phase I trial in patients with advanced leukemias. Merck also halted a recently initiated Phase I trial of MK-0457 in combination with dasatinib (Sprycel, Bristol-Myers Squibb Co.) in patients with CML or Philadelphia chromosome-positive ALL.
"The clinical team currently is working to confirm the data from all sites," McConnell told BioWorld Today, "to fully understand" the safety findings and determine whether MK-0457 treatment is related to the observed safety issue. In the meantime, patients already enrolled in the studies can continue treatment with MK-0457, provided they are monitored for QTc prolongation.
The news made only a small dent in Vertex's stock (NASDAQ:VRTX), which closed Wednesday at $23.54, down $1.03, and is expected to have no impact "that we are aware of" on the company's potential $384 million collaboration with Merck, signed in June 2004, McConnell said, adding that "Merck is committed to the program." (See BioWorld Today, June 23, 2004.)
The Whitehouse Station, N.J.-based pharma firm has said its strategy in the Aurora kinase collaboration is to develop multiple drug candidates against different tumor types. It previously discarded one candidate generated from the alliance, VX-667, which was discontinued after failing to meet pharmacokinetic objectives in a Phase I study, but intends to move forward with another compound, VX-689, set to begin a Phase I trial early next year in advanced and/or refractory solid tumors.
MK-0457 is the most advanced Aurora kinase inhibitor to date, though several other candidates are moving forward in that space. South San Francisco-based Rigel Pharmaceuticals Inc. and partner Darmstadt, Germany-based Merck Serono SA, which recently expanded their worldwide Aurora kinase collaboration to include Japanese rights, are in Phase I trials with R763/AS703569, the lead drug, in leukemia and advanced tumors.
Also in Phase I are Cambridge, Mass.-based Millennium Pharmaceuticals Inc.'s MLN8327, Berkeley Heights, N.J.-based Cyclacel Pharmaceuticals Inc.'s CYC116 and South San Francisco-based Sunesis Pharmaceuticals Inc.'s SNS-314.
In other areas of its pipeline, Cambridge, Mass.-based Vertex continues to move forward with telaprevir, its protease inhibitor, which is expected to begin pivotal Phase III testing next year in hepatitis C virus.
The company is in Phase II development with VX-770, which is designed to restore the function of the cystic fibrosis transmembrane conductance regulator protein for treating cystic fibrosis, and with VX-702, a MAP kinase inhibitor aimed at rheumatoid arthritis.