Merck's investigational CCR5 antagonist vicriviroc did not demonstrate non-inferiority to optimized background therapy for treatment-experienced people in the VICTOR studies, researchers reported at CROI (abstract 54LB), leaving the drug's fate uncertain.
VICTOR-E3 and VICTOR-E4 were identical Phase III trials conducted in different geographical regions. Participants were randomly assigned to receive either 30 mg once-daily vicriviroc or placebo in combination with an optimized background regimen.
Enrollees had documented resistance to at least two antiretroviral drug classes, but were required to have at least two active drugs (i.e., not compromised by resistance) in their background regimen; about 60% had three or more active drugs. Approximately 40% used raltegravir and darunavir (Prezista), newer agents less subject to resistance.
In a combined modified intent-to-treat analysis of 721 participants with exclusively CCR5-tropic HIV, 64% of participants in the vicriviroc arms achieved viral load below 50 copies/mL at 48 weeks compared with 62% in the placebo arms, not a significant difference; CD4 cell gains were also similar. Therefore, vicriviroc did not demonstrate non-inferiority to the optimized background regimen.
Vicriviroc did show an advantage, however, for participants with fewer active drugs in their background regimen. Among people with two or fewer active background drugs, 70% in the vicriviroc arms and 55% in the placebo arms achieved undetectable viral load, a difference that did reach statistical significance.
The VICTOR studies raise the issue of how new antiretroviral drugs are tested in the era of highly effective ART. Presenter Joseph Gathe explained that with modern drugs, even many heavily treatment-experienced patients can construct suppressive regimens; in contrast, drugs approved in the past faced less stiff competition. Vicriviroc failed to work better than a potent background regimen that was already working well, but it was superior to a less active background.
"While these results are disappointing, it is becoming increasingly difficult for an additional HIV medicine to demonstrate a significant incremental benefit as the fourth or fifth drug added to optimized background therapy," said Merck's Lisa Dunkle. Prior to CROI, Merck informed investors that it does not plan to seek FDA approval of vicriviroc for treatment-experienced patients, though it will continue to evaluate the drug as first-line therapy.
Liz Highleyman (email@example.com) is a freelance medical writer based in San Francisco.