MEXICO CITY, Aug. 7, 2008 -- GlaxoSmithKline announced that a retrospective analysis of six clinical trials found that anti-HIV regimens containing EPZICOM (abacavir + lamivudine) were effective in treatment-naive patients regardless of baseline viral loads. One of the trials analyzed was a large study comparing treatment with
regimens containing EPZICOM versus regimens containing Truvada (tenofovir DF + emtricitabine) in treatment-naive patients with both high and low baseline viral loads. The analysis was presented today at the 17th
International AIDS Conference in Mexico City, Mexico.

GSK examined six clinical trials with 2,940 treatment-naive patients on regimens containing either EPZICOM or its individual components over 48 weeks of treatment, including the HEAT study, a head-to-head clinical trial
comparing EPZICOM to Truvada. Patients were analyzed according to baseline viral load (<100,000c/mL being low and greater than or equal to 100,000c/mL being high) and efficacy was determined by time to virologic failure. The definition of virologic failure was similar to that utilized in the ACTG 5202 study. At 48 weeks, 87-95% of all patients in the analysis did not meet the definition for virologic failure. An additional retrospective
analysis of the HEAT study found similar results in both EPZICOM- and Truvada-containing regimens regardless of baseline viral load.

The analysis was conducted after interim data from a single, ongoing study by the AIDS Clinical Trials Group (ACTG 5202) found results inconsistent with previous experience with EPZICOM. A routine review of
ACTG 5202 by the data safety monitoring board (DSMB) found that although both the EPZICOM and Truvada treatment arms were effective in reducing HIV viral load, a statistically higher rate of protocol-defined virologic
failure and protocol-defined safety endpoints were seen in patients with high screening viral loads in the EPZICOM-treatment arm. The rates of HIV viral load reduction with EPZICOM in the high viral load arm were lower than what has been reported in existing clinical data.

Following these findings, the DSMB recommended unblinding patients receiving EPZICOM in the high viral load arm. Affected patients were notified of the results by the physicians and provided the option to stay on EPZICOM if the patient was having success with the regimen. The DSMB recommended that study participants with lower screening viral loads continue on their assigned blinded regimen and be followed in the study without change. The ACTG 5202 trial is ongoing and patients in the high viral load arm have the option to continue in the study, whereas those in the lower viral load group continue in the trial and remain blinded to their regimens.

Study Analysis Explained

GSK's retrospective analysis included 48-week data from six clinical trials in 2,940 treatment-naive HIV patients. Patients were analyzed based on baseline HIV viral load (<100,000c/mL and greater than or equal to
100,000c/mL) with a primary efficacy endpoint of time to virologic failure measured using Kaplan-Meier analysis. Virologic failure was defined as confirmed viral load greater than or equal to 1,000c/mL at or after 16 weeks and before 24 weeks, or viral load greater than or equal to 200c/mL at or after 24 weeks. These are similar to the virologic failure criteria used in ACTG 5202 to assess the impact of screening viral load on virologic response.

The six clinical trials included in the analysis were CNA30024, CNA30021, ESS30009, SHARE, KLEAN and HEAT. The analysis examined EPZICOM-containing regimens in each study and the Truvada-containing
regimens in HEAT. Among all patients receiving EPZICOM in the six clinical trial analysis, 87-95% did not experience virologic failure by 48 weeks of treatment. In the HEAT study 87-90% of patients in both the EPZICOM and Truvada arms did not experience virologic failure by 48 weeks, regardless of baseline viral load (<100,000 and greater than or equal to 100,000c/mL).

A safety analysis was also conducted in the HEAT study using the ACTG 5202 safety endpoint criteria. The safety endpoint was defined as time to onset of first grade 3 or 4 sign, symptom, or lab toxicity at least 1 grade
higher than baseline, as used in ACTG 5202. In both treatment arms of the HEAT trial, 15% of patients had drug-related Grade 3-4 adverse events. Safety data from the HEAT analysis also found that both EPZICOM- and
Truvada-containing regimens were generally well-tolerated with few treatment discontinuations due to adverse events, (19% with Epzicom and 24%with Truvada).