Schering Plough announced last night that it has halted a phase II study of vicriviroc, its experimental CCR5 antagonist, in treatment-naïve patients owing to early viral load rebound in the patients receiving the drug. A study in treatment-experienced patients will continue, but the omens are not good for the further development of this drug – and for the prospect of multiple agents in the CCR5 antagonist class.
Earlier this week Glaxo SmithKline announced that it was calling a halt to phase III studies of its CCR5 antagonist aplaviroc in treatment-experienced patients due to one case of liver toxicity in these studies. Last month the company halted a phase IIb study of aplaviroc in treatment-naïve patients due to two cases of serious liver enzyme elevation.
GSK says it does not plan any further studies of aplaviroc, strongly suggesting that this product is now dead.
Schering Plough said that its own decision was “not based on hepatotoxicity or other significant safety issues in patients receiving vicriviroc in the study or in a second Phase II study in treatment-experienced HIV patients, which is continuing.” The Phase II study in U.S. treatment-experienced patients is being conducted by the NIH-sponsored AIDS Clinical Trials Group (ACTG) and is fully enrolled.
The company said that it discontinued its Phase II treatment-naïve study following a recommendation from the independent Data Safety Monitoring Board (DSMB), which has been meeting regularly to conduct reviews of the safety and efficacy data. The announcement implies that the vicriviroc/Combivir arm was already showing inferiority to the current standard of care Combivir/efavirenz, which was provided to the comparator arm in this study.
The increased incidence of detectable virus was only seen in some patients after several weeks of treatment. The study had been under way since spring 2004 in 23 centers in Europe and Canada, with 92 patients enrolled. Patients already enrolled in the treatment-naïve study will continue to receive vicriviroc until they can be switched to an alternative regimen in consultation with their physician. Clinical trial investigators for the study, their Ethics Committees and Health Authorities are being notified.