The United States Food and Drug Administration (FDA) granted accelerated approval of the new protease inhibitor darunavir on Friday. Darunavir, which was known as TMC114 during development and will be marketed as Prezista, will now be available for HIV-positive patients in the United States whose infection is not responding to treatment with other anti-HIV drugs.
This approval will come as good news for HIV-positive patients in the United States who have few treatment options available after failure of previous drug combinations.
The recommended dose for darunavir is 600mg twice a day. Each dose must be taken at the same time as 100mg ritonavir (Norvir) and with food. The small dose of ritonavir decreases the breakdown of darunavir in the liver, resulting in higher levels of the drug in the blood. Darunavir is produced in orange tablets containing 300mg of the active drug.
Darunavir is not yet approved for use in children, or in patients who have not taken any anti-HIV drugs before.
The approval of darunavir was granted after the drug’s manufacturer, Tibotec Inc., presented data from two randomised studies to the FDA. These studies, called TMC114-C213 (POWER 1) and TMC114-C202 (POWER 2), looked at the risks and benefits of the drug in patients with substantial treatment experience, finding that patients taking ritonavir-boosted darunavir had larger reductions in their viral loads than patients taking other ritonavir-boosted protease inhibitors.
Taken together, the two studies found that 70% of the patients taking darunavir had a viral load reduction of at least 1 log10 after 24 weeks. This was in contrast to only 21% of the patients taking another protease inhibitor. The patients taking darunavir also had larger increases in CD4 cell count (92 vs. 17 cells/mm3).
Both groups of patients took their protease inhibitors with other anti-HIV drugs, including nucleoside reverse transcriptase inhibitors (NRTIs), chosen on the basis of genetic testing. Almost half of the patients also took the fusion inhibitor T-20 (enfuvirtide, Fuzeon).
The main side-effects seen in the studies were diarrhoea, nausea and headache. Around 7% of the patients also had skin rashes. These were serious in a few cases.
Darunavir should not be taken with other drugs that are broken down through the cytochrome 3A system. These include many prescription and non-prescription drugs, as well as certain herbal products such as St John’s wort. Other drugs may need to be taken at non-standard doses with darunavir.
Accelerated approval is granted for drugs that are likely to have a significant benefit for patients, before all of the formal studies into its efficacy and safety have been completed.
As a condition of the accelerated approval, Tibotec has agreed to carry out more studies into darunavir’s activity, particularly in children and in patients with liver damage. Tibotec will also carry out more studies into interactions between darunavir and other drugs.
Approval of darunavir in the European Union is expected later this year.