Darunavir (DRV), also known as TMC114, was developed by Tibotec Pharmaceuticals and received accelerated approval by the United States Food and Drug Administration (FDA) in June 2006. In February 2007, darunavir was conditionally approved by the European Medicines Agency.



Two years after it granted darunavir accelerated approval, the U.S. FDA granted traditional approval. The traditional approval expands the indication for darunavir/rtv to include treatment-naïve patients and marks a major milestone both for Tibotec and the HIV community. Darunavir with ritonavir (rtv) is now an option for HIV-1 infected patients across the treatment spectrum in the U.S. and more recently also in the EMA, Canada, and many other countries. With the expanded indication, Tibotec is able to reach new communities of patients. Darunavir is an important treatment option for initial therapy as well as for those who have failed previous regimens. The dosage for treatment-naïve patients (those who have never been on HIV drug therapy) is a once-daily dose (800 mg darunavir, taken as two 400 mg tablets with 100 mg of ritonavir) - a simple regimen. Once-daily dosing regimens have been shown to increase patients' adherence to treatment. The darunavir/rtv once-daily regimen has shown good tolerability combined with high efficacy rates in clinical trials making darunavir/rtv an excellent option for treatment-naïve patients.



The FDA traditional approval is based on 48-week clinical trial data from two phase III trials TMC114-C214 (TITAN) and TMC114-C211 (ARTEMIS). The EU full approval was obtained in January 2008 following the renewal applications fulfilling all remaining specific obligations.



In the EU, darunavir 400 mg, co administered with low dose ritonavir is indicated in combination with other antiretroviral medicinal products for the treatment of human immunodeficiency virus (HIV 1) infection in antiretroviral therapy (ART) naïve adults. Darunavir 300 mg and 600 mg, co-administered with 100 mg ritonavir is indicated in combination with other antiretroviral medicinal products for the treatment of human immunodeficiency virus (HIV-1) infection in treatment experienced adult patients, including those that have been highly pre treated.



In December 2008, the U.S. FDA also approved the use of darunavir in children and adolescents together with two new formulations, the 75mg and the 150mg tablets. In June 2009, the use in children and adolescents was also approved by the EMA. This approval is based on clinical trial data from the phase II trial TMC114-C212 (DELPHI) in treatment-experienced children age 6 and older. Two other trials in children are ongoing: TMC114-TiDP29-C228 (ARIEL) in treatment-experienced children from the age of 3 years to 6 years and the TMC114-TiDP29-C230 (DIONE) trial in treatment-naïve adolescents.



TMC114 Clinical Trials



The two phase IIb controlled and randomized trials that supported darunavir's initial approval are POWER 1 (TMC114-C213) and POWER 2 (TMC114-C202). Main publications from the Phase IIb program are:

• Efficacy and safety of darunavir/rtv at week 48 in treatment-experienced patients with HIV-1 infection in POWER 1 and 2: a pooled subgroup analysis of data from two randomised trials. Published in Lancet (April 2007).

• 48 week (efficacy and safety data of darunavir/rtv 600/100 mg bid dose in early treatment-experienced, HIV-infected patients (TITAN). Published in Lancet (July 2007).
• 48 week efficacy and safety data of darunavir/rtv 800/100 mg qd dose in treatment-naïve, HIV-infected patients (ARTEMIS). Published in JAIDS (July 2008).