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New Head-to-Head Study Comparing LEXIVA® and Atazanavir Show Similar Efficacy and Lipid Changes

Additional Studies Evaluate a Lower Dose of Ritonavir® for Boosting LEXIVA

Sydney, Australia · July 25, 2007 /PRNewswire/ — A new study comparing two protease inhibitors used in the treatment of HIV patients showed similar efficacy and lipid effects between the two drugs. The head to head study evaluated the use of GlaxoSmithKline's (GSK) LEXIVA® (fosamprenavir calcium) given on an open-label, randomized basis to 106 antiretroviral-naïve patients versus the protease inhibitor atazanavir* (Reyataz®). These data, from a study known as ALERT, were presented today at the 4th International AIDS Society Conference (IAS) in Sydney, Australia.

A separate study, also presented at IAS, provides additional information on the efficacy and impact on lipids of LEXIVA with a lower dose of ritonavir—100mg instead of 200mg—once-daily in treatment-naïve patients. Ritonavir works with LEXIVA and other protease inhibitors to boost the medication level in the bloodstream making the protease inhibitor more effective in suppressing HIV.

LEXIVA is indicated in combination with other antiretrovirals for the treatment of HIV infections and is usually boosted with 200mg of ritonavir. A regimen of LEXIVA with a 100mg dose of ritonavir is not approved; however, it is currently being evaluated for use by the U.S. Food and Drug Administration.

ALERT Study Explained

ALERT (Atazanavir or LEXIVA with Ritonavir and Truvada) was an open-label, randomized study of 106 patients comparing the efficacy and safety of LEXIVA/r 1400mg/100mg to atazanavir (ATV/r) 300mg/100mg, each in combination with tenofovir and emtricitabine. Antiretroviral-naïve patients were randomized to either treatment arm and received medication once daily. The study monitored changes in viral load, total cholesterol, HDL, LDL and triglycerides. At week 48, both treatment arms showed comparable viral suppression, changes in lipid levels, incidence of adverse effects, and CD-4 cell count improvements.

• In the LEXIVA/r arm, 75 percent (40/53) had viral load <50c/mL and 79 percent (42/53) had viral load <400c/mL. This compared with 83 percent (44/53) [p=0.34] and 87 percent (46/53) of patients [p=0.30] taking atazanavir/r, respectively.
• Percent increase in median lipids at week 48 was also similar for both treatment arms. Results for the LEXIVA/r and atazanavir/r arms were, respectively: total cholesterol 11mg/dL vs. 27mg/dL, triglycerides 34mg/dL vs. 7mg/dL, HDL-cholesterol 5mg/dL vs. 11mg/dL, and LDL-cholesterol 4mg/dL vs. 4mg/dL.
• Mean CD4 cell count change from baseline was +170 cells/mm³ for LEXIVA/r vs. +183 cells/mm³ for atazanavir/r.

Treatment-related Grade 2-4 adverse events occurred in a similar proportion of patients in both arms with the exception of hyperbilirubinemia which occurred in 43 percent of the patients in the ATV/r arm and in none of the patients treated with LEXIVA.

Ritonavir Dosing Study Explained

This study was an open-label, randomized study in 115 antiretroviral-naïve patients that compared the effect of the 200mg boosted dose to the 100mg boosted dose on changes in regional fat mass and bone mineral density (BMD). Epzicom® (abacavir sulfate and lamivudine) was the nucleoside backbone in both groups. The primary efficacy endpoints were HIV RNA <400 copies/mL at 48 weeks and the proportion of patients who experienced drug related discontinuations at week 48 (total N = 115).

Specifically the study showed:

• 84 percent of the patients in the ritonavir 100mg arm compared with 67 percent of the patients in the ritonavir 200mg arm achieved HIV RNA < 400 copies/mL at week 48 (p = 0.026).
• Fat changes in the upper limbs for patients treated with LEXIVA/r 200mg (n=43) versus LEXIVA/r 100/mg (n=44) was 16 percent vs. 11 percent, lower limbs (14 percent vs. 9 percent) and trunk (32 percent, vs. 18 percent).
• Changes in fasting lipids were similar between treatment groups.
• Although clinically meaningful (> 20 percent) declines in arm and leg fat and increases in trunk fat occurred in both groups of patients, they occurred less frequently in patients treated with LEXIVA plus 100mg ritonavir once per day (difference not statistically significant).
• Changes in BMD were small (<1 percent) in both study arms at 48 weeks.

Overall, treatment with LEXIVA/r was generally well-tolerated. The most commonly reported adverse events were Grade 1 and included diarrhea (30 percent), nausea (20 percent), and vomiting (10 percent). There were no virologic failures or discontinuations due to adverse events.

LEXIVA Indication Statement and Background

LEXIVA is indicated for the treatment of HIV infection in combination with other antiretroviral medications. The following points should be considered when initiating therapy with LEXIVA plus ritonavir (LEXIVA/r) in protease inhibitor (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.

The recommended dosing for LEXIVA is:

• Therapy naïve adults
  • LEXIVA 1400mg twice daily
  • LEXIVA 1400mg once daily plus ritonavir 200mg once daily
  • LEXIVA 700mg twice daily plus ritonavir 100mg twice daily
• Protease inhibitor experienced adults
  • LEXIVA 700mg twice daily plus 100mg ritonavir twice daily

LEXIVA was approved by the FDA for use in the US in 2003. It is the first PI to offer flexible dosing options (for PI-naïve patients) with no food or water restrictions.

Important Safety Information about LEXIVA

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

Patients should not take LEXIVA if they have had an allergic reaction to LEXIVA or AGENERASE® (amprenavir). High blood sugar, diabetes or worsening of diabetes, and bleeding in hemophiliacs have occurred in some patients taking protease inhibitors. When a patient starts taking HIV medicines, his immune system may get stronger and could begin to fight infections that have been hidden in his body, such as pneumonia, herpes virus, or tuberculosis. If a patient has new symptoms after starting his HIV medicines, he should tell his doctor. Changes in body fat may occur in some patients taking antiretroviral therapy. The cause and long-term health effects of these conditions are not known at this time. Skin rashes can occur in patients taking LEXIVA. Rarely, rashes were severe or life threatening. Opportunistic infections can develop when a patient has HIV and his immune system is weak. It is very important that patients see their healthcare provider regularly while taking LEXIVA to discuss any side effects or concerns. Most common side effects in clinical studies were diarrhea, headache, nausea, rash, and vomiting. In most cases, these side effects did not cause people to stop taking their medicine.

For full prescribing information for LEXIVA, please visit www.treathiv.com.

LEXIVA was co-discovered by GlaxoSmithKline and Vertex Pharmaceuticals Incorporated.

About GlaxoSmithKline

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 www.LEXIVA.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 2004, GlaxoSmithKline donated more than $372.5 million worth of prescription drugs to 475,000 patients. For more information, visit www.bridgestoaccess.gsk.com or call 1-866-PATIENT.

About Vertex

Vertex Pharmaceuticals Incorporated is a global biotechnology company committed to the discovery and development of breakthrough small molecule drugs for serious diseases. The Company's strategy is to commercialize its products both independently and in collaboration with major pharmaceutical companies. Vertex's product pipeline is principally focused on viral diseases, inflammation, autoimmune diseases and cancer. Vertex co-discovered the HIV protease inhibitor, LEXIVA, with GlaxoSmithKline.

Vertex's press releases are available at www.vrtx.com.

* Atazanavir is known by the trade name Reyataz® and is made by Bristol-Myers Squibb.

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