PRNewswire - October 30, 2004

According to 48-week data presented at ICAAC:

• Levels of HDL-C, were increased in patients taking LEXIVA who had low HDL-C at baseline.
• There were minimal changes in TC/HDL-C ratios.

Additional results seen at 120 weeks were presented last week at the International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV.

LEXIVA is the first PI with flexible dosing and no food or fluid restrictions, which may help simplify ART regimens for some patients.

WASHINGTON -- Increases in HDL cholesterol (HDL-C) were reported among HIV-infected patients on ART regimens containing the protease inhibitor (PI) LEXIVA® (fosamprenavir calcium). Minimal changes were seen in total cholesterol (TC)/HDL-C ratios, according to a study presented here today at the 44th Interscience Conference on Antimicrobial Agents and Chemotherapy. LEXIVA was approved for marketing by the FDA in Oct. 2003 and is indicated for the treatment of HIV infection in adults in combination with other antiretroviral medication. It is the first PI to offer flexible dosing options with no food or fluid restriction. The following points should be considered when initiating therapy with LEXIVA/ritonavir (LEXIVA/r) in PI-experienced patients: the PI-experienced patient study was not large enough to reach a definitive conclusion that LEXIVA/r and lopinavir/ritonavir are clinically equivalent. Once-daily administration of LEXIVA plus ritonavir is not recommended for PI-experienced patients. LEXIVA was co-discovered by GlaxoSmithKline (GSK) and Vertex Pharmaceuticals (NASDAQ:VRTX) .

"Increases in HDL, the so-called 'good' cholesterol, were observed in an analysis of 48-week data from the NEAT study, and follow the results of 120- week data from boosted LEXIVA in the SOLO study presented here last week at the International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV," said Doug Manion, M.D., vice president for HIV Clinical Research for the Infectious Diseases Medicines Development Center (MDC) for GSK.

The percent with TC/HDL-C ratio >6.5 remained unchanged in the LEXIVA group and increased in the nelfinavir (NFV) group.

The NEAT Study

In the study presented at ICAAC, lipid levels were analyzed for patients from the NEAT trial, a 48-week randomized study. At 48 weeks, 109 patients in the regimen containing LEXIVA, and 40 patients in the regimen containing NFV were available for analysis. Baseline HDL-C was low (<40mg/dL) in both groups.

At 48 weeks:

• Mean percent increase from baseline in HDL-C was 37 percent in the group taking LEXIVA compared to 22 percent in the group taking NFV.
• Mean percent increase from baseline in TC was 31 percent in the group taking LEXIVA compared to 29 percent in the NFV group, while median changes in TC/HDL-C ratios were seen in 1 percent and 12 percent respectively.

All patients also received the nucleoside reverse transcriptase inhibitors ZIAGEN® (abacavir, ABC) and EPIVIR® (lamivudine, 3TC) BID.

The SOLO Trial

The data presented at ICAAC follow the results presented last week at the International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV. In that study, lipid data at 120 weeks were analyzed for 174 subjects on an ART regimen that included 1400 mg of LEXIVA plus 200 mg ritonavir (LEXIVA/r) dosed once a day. At baseline, median HDL-C was 36 mg/dL. At 48 weeks, HDL increased a median of 8 mg/dL (21 percent) with further median increases of 12 mg/dL (36 percent) at week 96 and 13 mg/dL (35 percent) at week 120. Median changes in TC/HDL-C ratios were 0.37 at week 48, after which median changes showed a decrease (-0.01 at week 96 and -0.07 at week 120).

The proportion of subjects with low HDL-C decreased from 62 percent at baseline to 31 percent at 120 weeks, while the proportion of patients with a TC/HDL ratio above 6.5 did not change over time (11 percent at baseline, 9 percent at week 120). All patients also received the nucleoside reverse transcriptase inhibitors ZIAGEN® (abacavir, ABC) and EPIVIR® (lamivudine, 3TC) BID.

Treatment with LEXIVA and ritonavir has resulted in the increase in concentration of triglycerides. Cholesterol testing should be performed prior to initiating therapy with LEXIVA and at periodic intervals during therapy.

LEXIVA may be dosed three different ways in ART-naive patients: 1) two 700 mg tablets twice daily (BID), 2) two 700 mg tablets once daily (QD) in combination with two 100 mg capsules of ritonavir QD (LEXIVA/r QD), or 3) one 700 mg tablet BID in combination with one 100 mg capsule of ritonavir BID (LEXIVA/r BID). For PI-experienced patients, the recommended dose is one 700 mg tablet BID in combination with one 100 mg capsule of ritonavir BID.

The FDA approval of LEXIVA was based on experience in more than 1,200 HIV- infected people -- both ART-naive and PI-experienced patients -- who participated in three pivotal Phase III trials to test the safety and efficacy of LEXIVA with and without ritonavir. In all three trials, study drugs were taken as part of combination therapy that included two nucleoside reverse transcriptase inhibitors.

Important Safety Information about LEXIVA

HIV medicines do not cure HIV infection/AIDS or prevent passing HIV to others.

LEXIVA is contraindicated in patients with previously demonstrated clinically significant hypersensitivity to any of the components of this product or to amprenavir. Hyperglycemia, new onset or exacerbations of diabetes mellitus, and spontaneous bleeding in hemophiliacs have been reported with protease inhibitors. Redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and "cushingoid appearance" have been observed in patients receiving antiretroviral therapy. The causal relationship, mechanism, and long-term consequences of these events are currently unknown.

LEXIVA is contraindicated with ergot derivatives, cisapride, pimozide, midazolam, and triazolam. If LEXIVA is coadministered with ritonavir, flecainide and propafenone are also contraindicated. The most common adverse events seen in clinical trials with LEXIVA were diarrhea, nausea, vomiting, headache and rash.

GlaxoSmithKline is one of the world's leading research-based pharmaceutical and healthcare companies and an industry leader in HIV research and therapies. The company is engaged in basic research programs designed to investigate new targets to treat HIV. For full prescribing information please go to http://www.treathiv.com/ .

GSK's Bridges to Access program can help provide qualified individuals with access to GSK's antiretroviral medications, as well as help identify insurance or other support for medications. Patients may be eligible for this program if they are not eligible for prescription drug benefits through any other private or public insurer, payer, or program. In 2003, GlaxoSmithKline donated more than $205 million worth of prescription drugs to 400,000 patients. For more information, visit http://www.bridgestoaccess.gsk.com/ or call 1-866-PATIENT.

Source: GlaxoSmithKline

CONTACT: Mary Faye Dark of GlaxoSmithKline,
cell, 10-29 through 11-1, +1-919-451-4832,
or office, +1-919-483-2839; or

Beth Schlesinger of Public Communications Inc.,
pager, 10-29 through 11-1, +1-800-759-8888, PIN 1050707, or
office, +1-312-558-1770

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