Maraviroc recommended for accelerated approval in the US

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A key advisory committee to drug regulatory authorities in the United States has unanimously recommend the accelerated approval of the investigational antiretroviral drug maraviroc (Celsentri).

If approved by the Food and Drug Administration (FDA), maraviroc will become the first licensed drug from a novel class of antiretrovirals known as CCR5 inhibitors which prevent HIV’s entry into CD4 cells by blocking the CCR5 co-receptor on the cell’s surface.

The recommendation of the FDA’s Antiviral Drug Adivisory Committee was based on 24-week results from the MOTIVATE studies involving highly treatment experienced individuals. These results showed that significantly more patients who received maraviroc, with an optimised background of antiretroviral drugs, achieved a a viral load below 400 copies/ml and 50 copies/ml compared to individuals who received optimised background plus a placebo. Furthermore, patients in the maraviroc arms of the MOTIVATE studies also experienced greater increases in their CD4 cell count compared to the patients who were randomised to receive a placebo.

Glossary

CCR5

A protein on the surface of certain immune system cells, including CD4 cells. CCR5 can act as a co-receptor (a second receptor binding site) for HIV when the virus enters a host cell. A CCR5 inhibitor is an antiretroviral medication that blocks the CCR5 co-receptor and prevents HIV from entering the cell.

Food and Drug Administration (FDA)

Regulatory agency that evaluates and approves medicines and medical devices for safety and efficacy in the United States. The FDA regulates over-the-counter and prescription drugs, including generic drugs. The European Medicines Agency performs a similar role in the European Union.

placebo

A pill or liquid which looks and tastes exactly like a real drug, but contains no active substance.

CD4 cells

The primary white blood cells of the immune system, which signal to other immune system cells how and when to fight infections. HIV preferentially infects and destroys CD4 cells, which are also known as CD4+ T cells or T helper cells.

receptor

In cell biology, a structure on the surface of a cell (or inside a cell) that selectively receives and binds to a specific substance. There are many receptors. CD4 T cells are called that way because they have a protein called CD4 on their surface. Before entering (infecting) a CD4 T cell (that will become a “host” cell), HIV binds to the CD4 receptor and its coreceptor. 

CCR5 inhibitors have had a difficult clinical development. GlaxoSmithKline terminated development of its drug after cases of liver failure were observed, and Schering Plough suspended research into its agent after some patients experienced an early rebound in their viral load.

Although the MOTIVATE studies did not find that patients taking maraviroc had a significantly increased risk of cancer, liver problems, or mortality than the placebo arms, its development was also troubled. There were fears that CCR5 inhibitors may have serious liver toxicities as a class side-effect as a patient taking maraviroc experienced liver failure, although the clinical trial’s monitoring board concluded that patient factors were the likely cause. Research into the drug as a once-daily treatment for treatment-naïve individuals was stopped as the drug did not prove itself to be non-inferior to the recognised standard of HIV care.

Full, 48-week results from the MOTIVATE studies will be submitted to the FDA later this year, and if these prove satisfactory to the regulatory authorities, its formal approval will follow.