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FDA To Consider Approval Of First CCR5 Antagonist Against HIV/AIDS

Article Date: 23 Apr 2007

An advisory panel of the US Food and Drug Administration (FDA) is meeting tomorrow to decide whether to recommend approval of Pfizer's HIV/AIDS drug Maraviroc for patients already taking other drugs. If approved, it will be the first drug available in the class called CCR5 antagonists.

The FDA does not have to follow the panel's recommedations, but it usually does.

Many HIV drugs fight the virus from inside infected white blood cells. CCR5 antagonists stop the virus from getting into cells by blocking the main entry point common to most people who have the infection.

CCR5 stands for chemokine (C-C motif) receptor 5. HIV uses it as a co-receptor to get into target cells: the CD4 T-cells or helper cells, the main coordinators of the immune system.

When the co-receptor "sees" the HIV virus it signals to the main CD4 cell receptor to allow the HIV antigen into the target T-cell.

By blocking the CCR5 co-receptor, CCR5 antagonists stop strains of HIV known as "R5-tropic", an HIV variant that is common in earlier infection. However, as the disease progresses, the virus adapts to use an alternative entry point, the CXR4 receptor.

In February, Pfizer announced that marketing authorization applications for Maraviroc were receiving accelerated review in both the US and Europe.

Accelerated reviews are granted to drugs that may offer significant improvements over current therapies, if approved.

During development Maraviroc was known as UK-427857.

The marketing applications for Maraviroc are supported by efficacy and safety data from two phase 3 trials.

Named MOTIVATE-1 and 2 (Maraviroc plus Optimized Therapy In Viremic Antiretroviral Treatment-Experienced patients), the trials show 24 weeks of data comparing Optimized Background Therapy, with or without Maraviroc, in over 1,000 highly treatment-experienced patients with CCR5-tropic HIV-1.

The HIV virus was suppressed in 45 per cent of the patients, compared with 23 per cent who took a placebo. Maraviroc and the placebos were taken in combination with other drugs.

According to Pfizer, these trial results have been accepted for presentation at a forthcoming HIV conference.

CCR5 antagonists have raised safety concerns in the past. Earlier drugs under development were linked to lymphoma and liver damage.

These risks did not appear to be significant in the Pfizer studies, but according to media reports, the FDA reviewers are concerned about modest increases in liver damage.

When they submitted the marketing application, John LaMattina, president, Pfizer Global Research and Development, said:

"There is a profound global need for new medicines to help HIV/AIDS patients."

"We expect that CCR5 antagonists, like Maraviroc, will become critically important new treatment options for patients who are resistant or intolerant to their current HIV/AIDS therapies," he added.

Other drug companies are also working on CCR5 antagonists.

Nobody knows what the long term effect of using CCR5 antagonists will be. Some have speculated that it will accelerate the development of new strains of HIV that use other entry points.

Early trials have suggested not, but it highlights the importance of keeping an eye on the impact of the drug over the coming years should it pass the FDA and European approval.

According to researchers on the Pfizer trials, the priority now is to get the drug to the people who are running out of options. The longer term effects will not be known until the drug has been used for 5 to 10 years.

Written by: Catharine Paddock
Writer: Medical News Today


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