Bristol-Myers Squibb has reported positive trial results for BMS-660368, the first HIV drug to block the first stage of the virus’s entry into host cells.
The phase IIb trial showed that BMS-663068 was as effective as a boosted protease inhibitor regimen – BMS‘ Reyataz (atazanavir sulfate) plus ritonavir – when given to treatment-experienced HIV-1 patients.
After 24 weeks of treatment with the new drug candidate, between 69 and 80 per cent of this pre-treated population had undetectable levels of HIV in the blood, compared to 75 per cent of the Reyataz group.
BMS-663068 is an orally-active prodrug that is converted in the body into another compound (BMS-625629) that blocks the attachment of HIV to CD4+ T cells as well as the entry of the virus.
HIV entry is a three stage process, consisting of attachment to the CD4 receptor, binding to a co-receptor such as CCR5 or CXCR4, and finally fusion with the T cell membrane to allow the viral particles to be injected into the cell interior.
Other HIV entry inhibitors are available, such as ViiV Healthcare’s Selzentry/Celsentri (maraviroc) which blocks CCR5 binding and Roche’s Fuzeon (enfuvirtide) which targets the final fusion stage, but BMS-660368 is the first to block the initial attachment of the virus.
While HIV is now considered an infection that can be managed with therapy, often allowing patients to survive for a near-normal lifespan, over time resistance to existing drug classes can develop, while tolerability issues can interfere with therapy.
The addition of a third class of entry inhibitor could provide an additional treatment option for these patients, according to BMS-663068 trial investigator Jacob Lalezari, who is assistant clinical professor of medicine at UCSF/Mount Zion Hospital in the US.
“The data suggest that BMS-663068 is potentially as effective as one of the current standards of care and may provide another method of suppressing the virus in treatment-experienced patients,” he said.