The Pharmaceutical Journal
Vol 278 No 7443 p303
17 March 2007

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News summary

Initial data on CCR5 inhibitor for HIV look promising

A new class of anti-HIV drug, the orally available CCR5 entry inhibitor maraviroc, looks promising in initial 24-week data (US and Canada, Europe, Australia, and North America) first presented at the 14th Conference on Retroviruses and Opportunistic Infections in Los Angeles last month.

The MOTIVATE 1 and 2 studies are parallel 96-week trials conducted largely inside and outside the US, respectively, in a total of 1,076 heavily treatment-experienced patients on failing regimens. Howard Mayer, Pfizer’s global clinical leader on the development of maraviroc, said principal eligibility requirements were previous treatment with triple class therapy and a viral load >=5,000 copies/mL HIV-1 RNA.

HIV enters a cell by binding to a CD4 receptor, and then to either a CCR5 or CXCR4 coreceptor. The generally accepted view is that people who are recently infected have R5-tropic virus that uses the first coreceptor, and the X4-tropic variant emerges as disease progresses, but understanding of viral tropism remains incomplete and controversial.

Maraviroc only works against R5-tropic virus, so patients were screened for viral tropism; only those who were exclusively R5-tropic (56 per cent) were enrolled. Patients were prescribed an optimised background therapy and then randomised to placebo or 300mg of maraviroc administered once or twice a day (reduced with some regimens for pharmacodynamics reasons).

“Patients receiving maraviroc were twice as likely, in both studies independently, to achieve an undetectable HIV-1 RNA [<400 copies/mL] compared with the best available regimen. The studies were remarkably consistent in this regard,” said Dr Mayer. “Patients [in the maraviroc group] had essentially double the gain in their CD4+ T cells compared with patients who only received the best available regimen alone.

“Even though patients on maraviroc were on therapy longer because they didn’t fail as much as patients in the placebo groups, the adverse events profile looked remarkably similar,” he said.

Daniel Kuritzkes, director of AIDS Research at Brigham and Women’s Hospital in Boston, said the findings were important for people who need salvage therapy regimens. “Even though we have new protease drugs like tipranavir and darunavir, there are already large numbers of patients who have virus that is partly resistant to those protease inhibitors. Many people don’t want to be on an injectable, so T-20 [Fuzeon] is not an option for them,” he said.

Rosy Weston, pharmacy team leader sexual health and HIV at St Mary’s NHS Trust Hospital, London, commented: “Clearly UK clinicians are excited about the recent data on maraviroc, but there is still much uncertainty over its best place in therapy and the practical issues of availability and interpretation of tropism assays.”

Pfizer is seeking market approval for maraviroc in the US and Europe, with US approval likely in June. An expanded access programme is currently available to qualified patients throughout the world.