Maraviroc, the first of a new class of anti-HIV drugs called chemokine antagonists, or CCR5 inhibitors, yesterday received scientific approval from the European Union’s drug regulatory body, the EMEA, and could be available for prescription by November.
Maraviroc, which will be marketed as Celsentri, will be prescribed for treatment-experienced patients who have only CCR5-tropic virus (HIV which uses the CCR5 receptor to gain entry to CD4 cells).
CCR5 inhibitors block the CCR5 receptor, making it impossible for HIV to lock onto this target. Blocking the receptor means that HIV can infect fewer of its target cells.
HIV which can only use the CCR5 receptor is the dominant population in HIV-positive people during the early stages of HIV disease; the HIV population begins to switch to make use of both the CCR5 and CXCR4 receptors as the CD4 cell count falls, and faster CD4 cell decline is associated with the emergence of a predominantly CXCR4-tropic virus population.
Maraviroc has been approved on the basis of two studies in highly treatment-experienced patients with CCR5-tropic virus, MOTIVATE 1 and 2, which showed that more than half of patients who received the drug with a background regimen optimised by resistance testing achieved a viral load below 400 copies after 24 weeks.
Patients in the two studies had resistance to at least one drug in each class of antiretrovirals, and resistance to two protease inhibitors. However the license given to maraviroc in Europe is broad, specifying only that the drug can be used in `treatment-experienced` patients.
In comparison, Prezista (darunavir boosted by low dose ritonavir) was approved in Europe for treatment-experienced patients who had failed more than one protease inhibitor-containing regimen.
After receiving scientific approval from the EMEA's Committee for Medicinal Products for Human Use this week, the drug now awaits formal marketing approval from the European Commission, which must be issued within 90 days. Maraviroc will remain available through an expanded access programme from manufacturer Pfizer until it is available for prescription in European countries eligible for the programme.
Further data from the MOTIVATE studies elucidating the contribution of other drugs to treatment responses are due to be presented next week at the International AIDS Society conference in Sydney. Results from a 48-week study of maraviroc in treatment-naïve patients will also be presented.
In the United States maraviroc still awaits final approval from the US Food and Drug Administration. In June the FDA issued an approvable letter for the drug, which means that whilst in principle the drug can be approved, the FDA still requires more information before finalising prescribing information (known in the US as `labelling`) for the drug.
The FDA has asked for further information about liver toxicity observed in trials of the drug, as well as infections seen in those studies. There has also been speculation that the FDA wants more information about the performance of the Trofile tropism assay. The Trofile assay is used to screen out patients who have mixed-tropic or CXCR4-tropic virus.