The protease inhibitor darunavir (Prezista, TMC 114) has been given scientific approval for use in combination with low-dose ritonavir in treatment-experienced HIV-positive people in the European Union, the European Medicines Agency announced today. Formal marketing approval will follow in February 2007.
Darunavir has been approved for twice daily dosing at 600mg, combined with 100mg of ritonavir. It is indicated for use in highly pre-treated adult patients who have failed more than one regimen containing a protease inhibitor. Genotypic or phenotypic resistance testing, together with consideration of previous treatment history, should be used to determine whether darunavir/ritonavir should be used.
The drug has been approved at a relatively early stage in its development history, as in the United States.
Twenty-four week results from two phase IIB studies of Prezista that compared two different doses of the drug with the effects of other protease inhibitors in treatment-experienced patients were the basis for this drug approval. Combined analysis of the POWER 1 and 2 studies showed that 45% of those who received darunavir/ritonavir had viral load below 50 copies after 24 weeks of treatment with the drug, and a similar proportion of those still on treatment at week 48 had viral load below 50 copies.
Recently presented analyses of these studies have also shown response to darunavir does not appear to vary according to the previous protease inhibitors used, and that HIV needs to accumulate up to 11 different mutations in its protease enzyme in order to become resistant to darunavir. The drug was designed to have a high barrier to development of resistance, says its manufacturer Tibotec, and is likely to replace its less well tolerated competitor tipranavir (Aptivus) as the salvage therapy drug of choice.
Darunavir, in combination with ritonavir, is currently in Phase III comparative clinical trials versus lopinavir/ritonavir in treatment-experienced (TITAN, 600mg darunavir/100mg ritonavir twice daily) and treatment-naïve patients (ARTEMIS, 800mg darunavir/100mg ritonavir once daily).