The Shanghai-based Target Pharmaceutical company announced yesterday that it has signed the first stage of an international development and marketing agreement for an investigational CCR5 inhibitor, nifeviroc, with the Australian drug company Avexa.
CCR5 is a receptor on the surface of cells that HIV can use in order to gain entry. Blockade of the CCR5 receptor is an important target for drug discovery, but so far only one company, Pfizer, has been able to bring a CCR5 inhibitor project to fruition.
Pfizer’s product, maraviroc, is now in phase III studies and is expected to receive a license for use in treatment-experienced patients before the end of 2007 in Europe and the United States.
Two other CCR5 inhibitors have run into trouble. Trials of a compound developed by Glaxo SmithKline, called aplaviroc, were halted after two cases of severe liver toxicity. Development of Schering Plough’s vicriviroc was put on hold after cases of early viral rebound in a phase II study. Concerns about a class-wide predisposition to liver toxicity emerged after a serious case of liver toxicity in one patient receiving maraviroc.
Earlier fears of a class-wide toxicity problem have been quelled by the 24-week results of the MOTIVATE 1 & 2 studies of maraviroc in treatment-experienced patients and the lack of toxicity concerns raised by the Data Safety Monitoring Board in the 48-week phase III study of maraviroc in treatment-naïve patients (due to report results in the second half of 2007).
Nifeviroc was developed by Pei Gang of the Shanghai Life Sciences Institute and Ma Dewei of the Shanghai Institute of Organic Sciences. Phase I human studies are expected to begin next year. Chen Li, general manager of Target Pharmaceutical told China Daily: "The price will definitely be lower than foreign drugs."
Avexa is already testing a nucleoside analogue called apricitabine in phase IIb studies and has an HIV integrase inhibitor discovery programme. The company has been the subject of takeover and out-licensing speculation since it announced positive phase IIb results for apricitabine, with Gilead and Glaxo SmithKline mentioned as possible suitors, but chief executive Julian Chick said last month that the company intends to complete phase III trials of apricitabine on its own.