PRNewswire - October 30, 2004

At a Glance

According to preliminary data presented at ICAAC:

• Ritonavir (RTV) increased plasma PK parameters to a similar extent when co-administered with LEXIVA or APV.
• LEXIVA is the first PI with flexible dosing and no food or fluid restrictions, which may help simplify ART regimens for some patients.

WASHINGTON -- Results of pharmacokinetic (PK) comparisons between the protease inhibitors (PIs) LEXIVA® (fosamprenavir calcium) plus ritonavir (RTV), and AGENERASE® (amprenavir, APV) plus RTV were presented here today at the 44th Interscience Conference on Antimicrobial Agents and Chemotherapy.

LEXIVA, which was co-discovered by GlaxoSmithKline (GSK) and Vertex Pharmaceuticals (NASDAQ:VRTX) and was approved for marketing by the FDA in Oct. 2003, has shown to be similar in efficacy to AGENERASE, but offers a number of dosing benefits over AGENERASE.

LEXIVA is indicated for the treatment of HIV infection in adults in combination with other antiretroviral medications. 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 is another example of GSK's commitment to help simplify ART regimens for many patients. It is dosed as two small tablets twice daily (four total) or as two tablets daily in combination with RTV. LEXIVA is the first PI to offer flexible dosing options with no food or water restrictions, whereas AGENERASE requires dosing of eight capsules twice a day (16 total) and should not be taken with fatty foods," said Doug Manion, M.D., vice president for HIV Clinical Research for the Infectious Diseases Medicines Development Center (MDC) for GSK.

In the study presented at ICAAC, 32 healthy adult volunteers were randomized to two study arms. Study participants took 700 mg LEXIVA twice a day (BID) for 14 days followed by a 28 day "washout" period and then took 700 mg LEXIVA plus 100 mg RTV BID for 14 days. Following the washout period, they took 600 mg APV BID followed by a regimen of 600 mg APV plus 100 mg RTV BID, following the same schedule as the first arm. On day 14 of each treatment, blood samples were collected over 12 hours. The samples were analyzed for plasma levels of APV and measured to determine the effect of RTV in increasing plasma APV levels when administered with either LEVIXA or APV.

The study concluded RTV increased plasma APV PK parameters to a similar extent when co-administered with APV or LEXIVA. When either APV or LEXIVA were administered in combination with RTV, AUC increased approximately 3-fold and Cmin increased approximately 12-fold. Those taking LEXIVA plus RTV also experienced fewer gastrointestinal effects, especially nausea, skin rashes and neurological adverse events than patients taking APV plus RTV.

LEXIVA may be dosed three different ways in ART-naïve patients: 1) two 700 mg tablets 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-naïve 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. Treatment with LEXIVA and ritonavir has resulted in the increase in concentration of triglycerides. The most common adverse events seen in clinical trials with LEXIVA were diarrhea, nausea, vomiting, headache and rash.

AGENERASE is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection. The following points should be considered when initiating therapy with AGENERASE: in a study of NRTI-experienced, protease inhibitor-naïve patients, AGENERASE was found to be significantly less effective than indinavir. Mild to moderate gastrointestinal adverse events led to discontinuation of AGENERASE primarily during the first 12 weeks of therapy. There are no data on response to therapy with AGENERASE primarily during the first 12 weeks of therapy. There are limited data on response to therapy with AGENERASE in protease inhibitor-experienced patients. Because of the potential risk of toxicity from the large amount of the excipient propylene glycol contained in AGENERASE Oral Solution, that formulation is contraindicated in infants and children below the age of 4 years, pregnant women, patients with hepatic or renal failure, and patients treated with disulfiram or metronidazole.

AGENERASE Oral Solution should be used only when other protease inhibitor formulations are not therapeutic options. Amprenavir is a sulfonamide, and patients with a known sulfonamide allergy should be treated with caution. Caution should be exercised when administering AGENERASE to patients with hepatic impairment. In patients receiving protease inhibitors (including amprenavir), hyperglycemia, diabetes mellitus, acute hemolytic anemia and spontaneous bleeding in hemophiliacs have been reported. Severe and lifethreatening drug interactions could occur, and skin reactions including Stevens-Johnson syndrome have occurred with amprenavir. Redistribution/accumulation of body fat has been observed in patients receiving antiretroviral therapy. The causal relationship, mechanism, and long-term consequences of these events are currently unknown. 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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