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.
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.