ICAAC: 48-Week Data on Maraviroc (Selzentry) Reassuring

September 20, 2007

CHICAGO -- As clinical data accumulates, researchers are gaining confidence in a drug that blocks HIV from entering its target cells.

CHICAGO, Sept. 20 -- As the clinical accumulates, researchers are gaining confidence in a drug that blocks HIV from entering its target cells.

In 48-week data from a pivotal phase three clinical trial, the entry inhibitor maraviroc (Selzentry) continued to show potent efficacy against HIV strains that use the CCR5 receptor to invade T-cells, said Jacob Lalezari, M.D. of the University of California at San Francisco.

But equally important, he told attendees at the Interscience Conference on Anti-microbial Agents and Chemotherapy here, was that "no new or unexpected safety signal emerged."

That's likely to prove reassuring to clinicians, especially since another CCR5 inhibitor -- the investigational drug vicriviroc - has been plagued with an unexplained increase in malignancies. (See IAS: Cancers Worry Vicriviroc HIV Researchers)

Maraviroc was approved in August for the treatment of refractory HIV in adults.

The MOTIVATE-1 study on which Dr. Lalezari reported is one of two parallel trials in treatment-experienced adults with HIV. Participants in the trial had been on anti-retroviral therapy for a median of 14 years.

"This is a very treatment-experienced population indeed," he said.

The researchers enrolled 601 patients and randomized them to either placebo or maraviroc (either 150 mg daily or 150 mg twice daily).

In all cases, participants were also treated with what is called optimized background therapy -- the best possible regimen that their doctors could come up with.

The primary endpoint of the study was the change in HIV viral load from baseline to 48 weeks, Dr. Lalezari said.

The researchers found:

  • On average, patients on optimized background medication only saw their HIV RNA levels drop by less than a factor of 10 (a decline of 0.80 log10 in the number of copies of HIV RNA per milliliter of plasma).
  • Patients getting the once-daily dose of maraviroc had a drop of 1.66 log10 copies.
  • Those getting the twice-a-day dose had a drop of 1.82 log10 copies.

The reductions are similar to those seen at 24 weeks and reported at the retrovirus conference last year, Dr. Lalezari said. (See CROI: Maraviroc Has Double Success In Failing HIV Patients)

He also noted that there is a trend for daily dosing to be less effective than twice-daily dosing.

The study also found that the proportion of participants who reached an undetectable level of HIV - defined as fewer than 50 copies of HIV RNA per milliliter of plasma - was significantly greater for both maraviroc dosing schedules than for placebo.

Specifically, 46.8% of those on twice-daily maraviroc reached that level, compared with 41.8% of those getting the drug once a day, and 16.1% of those just on optimized background only. The differences from placebo were significant at P

Dr. Gulick said it will be particularly important to clinicians that the study saw no increased risk of malignancies or liver abnormalities.