96-Week Data From CASTLE Study Continue to Show Similar Efficacy Between Once-Daily REYATAZ® /Ritonavir and Twice-Daily Lopinavir/Ritonavir In Previously Untreated HIV-1 Infected Adult Patients

Business Wire, Oct 26, 2008

Data continue to show differences in gastrointestinal and lipid effects among study population

PRINCETON, N.J. -- Bristol-Myers Squibb Company (NYSE: BMY) today announced 96-week data from the CASTLE study, in which 74 percent of the 440 patients in the REYATAZ([R])(atazanavir sulfate)/r arm achieved an undetectable viral load, defined as HIV-1 RNA less than 50 copies/mL, compared with 68 percent of the 443 patients in the lopinavir/r arm. The difference between treatment arms may have been related to the 16 percent discontinuation rate in the REYATAZ/r arm and the 21 percent discontinuation rate in the lopinavir/r arm. These data from the CASTLE study were presented today at the joint 48th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC)/Infectious Diseases Society of America (IDSA) 46th annual conference in Washington, D.C.

"The 96-week analysis of the CASTLE study is consistent with the findings seen at 48 weeks, specifically the non-inferiority of once-daily REYATAZ/r compared to twice-daily lopinavir/r in treatment-naive patients," said Jean-Michel Molina, M.D., Hypital Saint Louis, Paris, France and from The University of Paris Diderot. "When initiating patients on antiretroviral combination therapy, it is important to include medicines with sustained activity against the virus, along with tolerability, to assist in the long-term treatment of patients with HIV-1."

The most common grade 2-4 adverse events occurring in greater than or equal to three percent of patients in the once-daily REYATAZ/r arm or the twice-daily lopinavir/r arm were diarrhea (2 percent and 12 percent, respectively), nausea (4 percent and 8 percent, respectively), jaundice (4 percent and 0 percent, respectively).

The REYATAZ([R])/r arm was associated with significantly lower increases from baseline compared to the lopinavir/r arm in total cholesterol, non-HDL cholesterol, and triglycerides at 96 weeks (p<0.0001). Two percent of patients in the REYATAZ/r arm and nine percent of patients in the lopinavir/r arm required initiation of lipid-lowering therapy while on study.

Safety events in this study were consistent with prior experience. No new or unexpected safety events were identified. Six deaths were reported in the REYATAZ/r arm (equal to one percent of total patients in REYATAZ/r arm) and five deaths were reported in the lopinavir/r arm (equal to one percent of total patients in lopinavir/r arm) at 96 weeks. Fourteen percent of patients in the REYATAZ/r arm and eleven percent of patients in the lopinavir/r arm experienced a serious adverse event.

About the CASTLE Study

The international, multi-center, open-label, 96-week CASTLE study randomized 883 treatment-naive patients infected with HIV-1. Four hundred and forty patients were randomized to receive REYATAZ 300 mg and ritonavir 100 mg (REYATAZ/r) once daily and 443 patients were randomized to receive lopinavir 400 mg and ritonavir 100 mg (lopinavir/r) 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 less than 50 copies/mL at 48 weeks. The CASTLE results demonstrated the non-inferiority of REYATAZ/r once daily versus lopinavir/r twice daily, each as part of HIV combination therapy in previously untreated HIV-1 infected adult patients.

Additional Study Results

A number of secondary endpoints were also measured with regard to efficacy, resistance, safety, tolerability, and lipid effects. Additional study results include:

Achievement of Undetectable Viral Load in Patients with High Baseline Viral Load

* In the study, 74% of the 223 patients with high baseline viral load ((=) 100,000 copies/mL) in the once-daily REYATAZ([R])/r arm achieved undetectable viral load at 96 weeks vs. 66% of the 225 patients with high baseline viral load in the twice-daily lopinavir/r arm.

Resistance

* Analysis of emergent resistance was conducted in patients with virologic failure (HIV-1 RNA (=) 400 copies/mL) and without baseline phenotypic protease-inhibitor resistance to the on-treatment protease inhibitor. One subject in each arm developed emergent major or minor PI substitutions with phenotypic resistance to REYATAZ/r and lopinavir/r, respectively, at Week 96.

Immunologic Response

* The mean increase in CD4 cell count from baseline at 96 weeks was similar between treatment arms with 268 cells/mm3 in patients in the REYATAZ/r arm and 290 cells/mm3 in patients in the lopinavir/r arm.

Safety and Tolerability

* 30% of patients in the REYATAZ/r arm and 32% of patients in the lopinavir/r arm experienced any grade 2-4 treatment-related adverse event.

* The incidence of treatment discontinuation due to adverse events was 3% in the REYATAZ/r arm and 5% in the lopinavir/r arm. The overall treatment discontinuation rates were 16% and 21% for REYATAZ/r and lopinavir/r arms, respectively.