You are here

FDA Approves Darunavir as Part of Combination Therapy for Treatment-Naïve Adults with HIV-1

Bridgewater, NJ (October 21, 2008) – The FDA has granted PREZISTA® (darunavir) tablets, a protease inhibitor, approval for an expanded indication for once-daily dosing as part of HIV combination therapy in treatment-naïve adults (those who have never taken HIV medication before). The FDA also granted traditional (full) approval to PREZISTA as twice-daily for use in treatment-experienced adult patients. PREZISTA was developed by Tibotec Pharmaceuticals and is marketed in the U.S. by Tibotec Therapeutics, a division of Ortho Biotech Products, L.P.

In June 2006, PREZISTA received accelerated approval for use in combination with other antiretrovirals (ARVs) in treatment-experienced adult patients, such as those with HIV-1 that is resistant to more than one protease inhibitor. Following today’s approval, PREZISTA, co-administered with 100 mg ritonavir (PREZISTA®), and with other antiretroviral agents, is indicated for the treatment of human immunodeficiency virus (HIV-1) infection.

This indication is based on analyses of plasma HIV RNA levels and CD4+ cell counts from two controlled phase 3 trials of 48 weeks duration in antiretroviral treatment-naïve and treatment-experienced patients and two controlled phase 2 trials of 96 weeks duration in clinically advanced, treatment-experienced patients.

In treatment-experienced patients, the following points should be considered when initiating therapy with PREZISTA®: treatment history and, when available, genotypic or phenotypic testing, should guide the use of PREZISTA®. The use of other active agents with PREZISTA® is associated with a greater likelihood of treatment response.

The risks and benefits of PREZISTA® have not been established in pediatric patients. No clinical studies have demonstrated the effect of PREZISTA® on clinical progression of HIV-1.

The traditional approval is based on 48-week data from the ARTEMIS and TITAN phase 3 non-inferiority studies and 96-week safety and efficacy data from the phase 2b POWER studies. Both ARTEMIS and TITAN studied the efficacy and safety of PREZISTA® vs. lopinavir® in combination with other ARVs.

The ARTEMIS study was conducted in treatment-naïve HIV-1-infected adult patients with an HIV viral load greater than or equal to 5,000 copies/mL. TITAN was conducted in lopinavir®-naïve, treatment-experienced adult patients and the POWER studies were conducted in clinically advanced, treatment-experienced adult patients with a high level of protease inhibitor resistance. In the TITAN and POWER studies, patients had evidence of ongoing HIV-1 replication despite antiretroviral therapy.

"Over the past two years, PREZISTA has made an important contribution to the care of treatment-experienced adults with HIV. The medical community welcomes the news that PREZISTA is now available as an effective, once-daily option as part of combination therapy for adults who have never taken HIV medications before,” said Calvin J. Cohen, M.D., M.Sc., clinical investigator and Research Director at Community Research Initiative of New England and Harvard Vanguard Medical Associates.

Forty-eight week results from ARTEMIS in treatment-naïve adults:

  • Eighty-four percent of patients in the PREZISTA® arm (n=343) reached an undetectable viral load ( The median change in CD4+ cell count from baseline was similar between PREZISTA® and lopinavir® arms (137 cells per cubic millimeter vs. 141 cells per cubic millimeter) (p = not statistically significant). Low rates of gastrointestinal adverse drug reactions (ADRs) were observed in the PREZISTA® arm.
  • Low rates of gastrointestinal adverse drug reactions (ADRs) were observed in the PREZISTA® arm.
  • Gastrointestinal ADRs of at least moderate intensity (≥ Grade 2) in ≥ 1 percent of patients were: diarrhea (6 percent vs. 13 percent), abdominal pain (4 percent vs. 5 percent), nausea (3 percent vs. 3 percent), vomiting (2 percent vs. 3 percent) respectively for PREZISTA® vs. lopinavir® arm.
  • In treatment-naïve adult patients, the most common ADRs (≥2 percent) reported of at least moderate intensity (≥Grade 2) in the PREZISTA® arm were diarrhea (6 percent), headache (5 percent ), abdominal pain (4 percent), nausea (3 percent), vomiting (2 percent), and rash (2 percent).
Forty-eight week results from TITAN in lopinavir®-naïve, treatment-experienced adults:
  • Seventy-seven percent of patients in the PREZISTA® arm (n=298) vs. 67 percent of patients in the lopinavir® arm (n=297) reached less than 400 copies/mL, (study demonstrated non-inferiority, p In treatment-experienced adult patients, the most common ADRs (≥2 percent) reported of at least moderate intensity (≥Grade 2) in the PREZISTA® arm were diarrhea (12 percent), nausea (7 percent), rash (6 percent), abdominal pain (5 percent), vomiting (4 percent), asthenia (3 percent), headache (2 percent), abdominal distension (2 percent), and dyspepsia (2 percent).
Ninety-six week results from POWER in clinically advanced, treatment-experienced adults:
  • Fifty-seven percent of patients in the PREZISTA® arm (n=131) vs. 10 percent of patients in the comparator protease inhibitor arm (n=124) achieved a virologic response defined as greater than or equal to a 1.0 log10 reduction (90 percent reduction) in viral load from baseline.
The latest recommendations from the International AIDS Society-USA Panel, which were published in the August 6, 2008 issue of the Journal of the American Medical Association, recommend PREZISTA as one of the initial treatment options as part of combination therapy for adults living with HIV.

“Tibotec is proud to reach this important milestone that makes PREZISTA available to those who are just starting HIV treatment for the first time,” said Glenn Mattes, President of Tibotec Therapeutics. “We look forward to continuing to provide treatment options that will add to the arsenal of anti-HIV therapies.”

Recommended dosing for treatment-naïve adult patients is 800 mg (two 400 mg tablets) taken with 100 mg ritonavir once daily. The new 400 mg tablet will be available by November 1. For treatment-experienced adult patients, the dosing for PREZISTA remains 600 mg taken with 100 mg ritonavir twice daily. PREZISTA must be taken with food and in combination with other ARVs. PREZISTA® is not recommended for use in patients with severe hepatic impairment.

Tibotec will discontinue production of the 300 mg tablet of PREZISTA as a result of decreasing demand following the introduction of the 600 mg tablet earlier this year. The 600 mg tablet allows treatment-experienced adult patients who currently take two 300 mg of PREZISTA twice daily to now take one 600 mg tablet twice daily.

Source: Johnson and Johnson

Recent Headlines

Despite older, sicker patients, mortality rate fell by a third in 10 years
Study finds fewer than half of trials followed the law
WHO to meet tomorrow to decide on international public heath emergency declaration
Study of posted prices finds wild variations and missing data
Potential contamination could lead to supply chain disruptions
Declining lung cancer mortality helped fuel the progress
Kinase inhibitor targets tumors with a PDGFRA exon 18 mutation
Delayed surgery reduces benefits; premature surgery raises risks
Mortality nearly doubled when patients stopped using their drugs