CASTLE Study Showed Similar Efficacy Between Once-Daily Reyataz® (atazanavir sulfate)/Ritonavir and Twice-Daily Lopinavir/Ritonavir at 48 Weeks in Previously Untreated HIV-Infected Adult Patients
Data also showed differences in gastrointestinal and lipid effects between REYATAZ/ritonavir and lopinavir/ritonavir among study population
MONTREAL, CANADA – (February 7, 2008) – Bristol-Myers Squibb Company (NYSE: BMY) today announced results from the CASTLE study, in which 300 mg of once-daily REYATAZ® (atazanavir sulfate) taken with 100 mg of ritonavir once daily (REYATAZ/r) showed similar antiviral efficacy to twice-daily lopinavir 400 mg and ritonavir 100 mg (lopinavir/r) in previously untreated adult HIV-1 infected patients at 48 weeks, as part of HIV combination therapy. In this study, patients in both arms were treated with TRUVADA (tenofovir 300mg/emtricitabine 200mg) once daily. Seventy-eight percent of the 440 patients in the REYATAZ/r arm met the primary endpoint of achieving undetectable viral load (defined as HIV-1 RNA less than 50 copies/mL) at 48 weeks, compared with 76 percent of the 443 patients in the lopinavir/r arm. CASTLE is the first large-scale, open-label, randomized study designed to demonstrate the non-inferiority of REYATAZ/r to lopinavir/r in previously untreated HIV-1 infected adult patients. Data from the CASTLE study were presented for the first time at the 15th Conference on Retroviruses and Opportunistic Infections (CROI) this week in Boston, Mass.
“The recent release of the 48 week CASTLE study provides clinicians with important and extremely relevant data on a once-daily regimen containing Reyataz with ritonavir boosting in combination with Truvada for anti-retroviral treatment naïve HIV+ individuals,” said Dr Roger LeBlanc MD FRCP (C) Montreal Chest Hospital, Immunodeficiency Unit, Montreal, Quebec, Canada. “There are now many treatment options available. This trial demonstrates this regimen to be metabolically safe and better tolerated, which will figure highly in the selection process for the best treatment option for our patients.” The most common grade 2-4 (moderate to severe) adverse events occurring in greater than or equal to three percent of patients in the once-daily REYATAZ® (atazanavir sulfate)/r arm or the twice-daily lopinavir/r arm were diarrhea (two percent and eleven percent, respectively), nausea (four percent and eight percent, respectively) jaundice (four percent and zero percent, respectively), increased bilirubin (six percent and zero percent, respectively) and rash (three percent and two percent, respectively).
The REYATAZ/r arm was associated with significantly lower increases from baseline compared to the lopinavir/r arm in total cholesterol, triglycerides and non-HDL cholesterol at 48 weeks. Two percent of patients in the REYATAZ/r arm and seven percent of patients in the lopinavir/r arm required initiation of lipid-lowering therapy in the study.
Safety events in this study were consistent with prior experience. Four deaths were reported in each treatment arm at 48 weeks; none were attributed to the study medications. Twelve percent of patients in the REYATAZ/r arm and ten percent of patients in the lopinavir/r arm experienced a serious adverse event.
Nine percent of patients in the REYATAZ/r arm and thirteen percent of patients in the lopinavir/r arm discontinued the study therapy before week 48.
About the CASTLE Study
The international, multi-center, open-label, 96-week CASTLE study randomized 883 treatment-naïve patients infected with HIV-1. Four hundred and forty patients were randomized to receive REYATAZ 300 mg and ritonavir 100 mg once daily and 443 patients were randomized to receive lopinavir 400 mg and ritonavir 100 mg twice daily, each in combination with a once-daily, fixed-dose combination of emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg. All patients had a baseline viral load of greater than or equal to 5,000 copies/mL; there was no CD4+ cell count restriction for study entry. The primary endpoint for the study was the proportion of patients with viral load of less than 50 copies/mL at 48 weeks.
About REYATAZ® (atazanavir sulfate)
REYATAZ® (atazanavir sulfate) is a protease inhibitor that has been studied extensively in both treatment-naïve and treatment-experienced HIV-infected patients and is designed to be administered once-daily in all patient populations. BMS recommends treating patients according to the product label. Currently, once-daily REYATAZ/r is indicated in Canada as part of combination HIV therapy in treatment-experienced patients. Unboosted REYATAZ is indicated to treat naïve patients in Canada, also as part of combination HIV therapy. However, if REYATAZ is combined with tenofovir in treatment-naïve patients—or certain other medications (eg, H2-recpetor antagonist, proton pump inhibitor, efavirenz), ritonavir must also be used.
About Bristol-Myers Squibb Canada
Bristol-Myers Squibb Canada is an indirect wholly-owned subsidiary of Bristol-Myers Squibb Company, a global pharmaceutical and related health care products company whose mission is to extend and enhance human life. Bristol-Myers Squibb Canada is a leading provider of medicines to fight cancer, cardiovascular and metabolic disorders, infectious diseases (including HIV/AIDS), nervous system diseases and serious mental illness. Bristol-Myers Squibb Company is listed on the New York Stock Exchange under the BMY symbol. Bristol-Myers Squibb Canada's operations are headquartered in Montréal, Québec.
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Bristol-Myers Squibb Canada