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Title: Interim Analysis of New Study Suggests Boosted Saquinavir Mesylate May Achieve Similar Levels of HIV Suppression to Boosted Lopinavir with a Favorable Lipid Profile

"Interim Analysis of New Study Suggests Boosted Saquinavir Mesylate May Achieve Similar Levels of HIV Suppression to Boosted Lopinavir with a Favorable Lipid Profile"

NUTLEY, NJ -- November 13, 2006 -- Encouraging results from an interim analysis of a new study suggest that the boosted protease inhibitor (PI/r) Invirase® 500 mg/r (saquinavir mesylate) has the potential to achieve comparable levels of viral suppression to the most commonly used PI, lopinavir/r (Kaletra®), with less lipid elevation. The results are from a planned 24-week interim analysis of 150 patients from the Gemini study, presented today at the Eighth International Congress on Drug Therapy in HIV Infection (HIV-8) in Glasgow, Scotland. These interim findings have potential beneficial implications for many HIV patients, who experience elevated cholesterol and triglycerides as common side effects of some antiretroviral (ARV) treatments. "These preliminary results suggest that boosted Invirase has the power to control the virus in treatment-naïve patients, while also managing their lipid profile," said Jihad Slim, MD, Infectious Disease Specialist at St. Michael's Medical Center in Newark, New Jersey and lead investigator of the Gemini study. "If the final results show that boosted Invirase maintains its ability to suppress the virus with a good lipid profile, it could become a preferred choice for some patients, especially those troubled by treatment side effects." Now that patients are remaining on effective HIV treatment for longer periods of time, managing the disease includes more than just treating the virus. It is essential that other factors that affect patient quality of life, such as high cholesterol and adverse gastrointestinal (GI) events, are considered. About the Gemini Study The Gemini study is a phase 3b multi-center, randomized, open-label, 48-week study, designed to evaluate the efficacy and safety of Invirase 500/r vs. lopinavir/r. These treatments are given at their approved twice-daily dosages in combination with two nucleoside reverse transcriptase inhibitors (emtricitabine/tenofovir [Truvada®], once daily) in treatment-naïve adults. The Gemini study enrolled 337 patients from Canada, France, Puerto Rico, Thailand and the United States. The primary efficacy endpoint of the trial is the number of patients with an HIV-1 RNA viral load of less than 50 copies/mL at week 48. There are two planned interim analyses. The interim data suggest that treatment-naïve patients on either boosted Invirase or boosted lopinavir achieved a comparable level of viral suppression (69.4% vs. 75.3%, respectively, with less than 50 copies/mL at week 24). The data also suggest favorable lipid profile as measured by increase in incidence of high cholesterol (greater than 200 mg/dl) or high triglycerides (greater than 400 mg/dl): • Only 4% of Invirase 500/r patients developed high cholesterol compared with 25% of lopinavir/r patients • Only 1% of Invirase 500/r patients developed high triglycerides compared with nine% of lopinavir/r patients Importantly, fewer GI adverse events were seen in the Invirase 500/r arm (14% vs. 23%) with lower incidence of nausea and diarrhea. About Invirase Invirase in combination with ritonavir and other antiretroviral agents is indicated for the treatment of HIV infection. The twice-daily administration of Invirase in combination with ritonavir is supported by safety data from the MaxCMin1 study and pharmacokinetic data. The efficacy of Invirase with ritonavir has not been compared against the efficacy of antiretroviral regimens currently considered standard of care. Invirase is contraindicated in patients with clinically significant hypersensitivity to saquinavir or to any of the components contained in the capsule. Invirase/ritonavir should not be administered concurrently with terfenadine, cisapride, astemizole, pimozide, triazolam, midazolam or ergot derivatives. Inhibition of CYP3A4 by saquinavir could result in elevated plasma concentrations of these drugs, potentially causing serious or life-threatening reactions, such as cardiac arrhythmias or prolonged sedation. Invirase when administered with ritonavir is contraindicated in patients with severe hepatic impairment. Patients with hepatic impairment have not been studied and caution should be exercised when prescribing saquinavir in this population. Concomitant use of Invirase with lovastatin or simvastatin is not recommended. Caution should be exercised if HIV protease inhibitors, including Invirase, are used concurrently with other HMG-CoA reductase inhibitors that are also metabolized by the CYP3A4 pathway (eg, atorvastatin). Concomitant use of Invirase and St. John's wort (hypericum perforatum) or products containing St. John's wort is not recommended. Garlic capsules should not be used while taking saquinavir as the sole protease inhibitor, due to the risk of decreased saquinavir plasma concentrations. For a complete list of drugs that should not be taken with saquinavir, please see TABLE 5 in the summary of complete product information. New-onset diabetes mellitus, exacerbation of preexisting diabetes mellitus and hyperglycemia have been reported during postmarketing surveillance in HIV-infected patients receiving protease-inhibitor therapy. No initial dose adjustment is necessary for patients with renal impairment. However, patients with severe renal impairment have not been studied, and caution should be exercised when prescribing saquinavir in this population. There have been reports of spontaneous bleeding in patients with hemophilia A and B treated with protease inhibitors. Elevated cholesterol and/or triglyceride levels have been observed in some patients taking saquinavir in combination with ritonavir. Redistribution/accumulation of body fat has been observed in patients receiving antiretroviral therapy. A causal relationship between protease inhibitor therapy and these events has not been established, and the long-term consequences are currently unknown. Varying degrees of cross-resistance among protease inhibitors have been observed. In clinical trials with saquinavir (1000 mg) in combination with ritonavir (100 mg) and other antiretrovirals, the grade 2, 3 and 4 adverse events occurring in ≥ 2% of 148 patients (considered at least possibly related to study drug or of unknown relationship): abdominal pain (6.1%), back pain (2%), bronchitis (2.7%), constipation (2%), diarrhea (8.1%), diabetes mellitus/hyperglycemia (2.7%), dry lips/skin (2%), eczema (2%), fatigue (6.1%), fever (3.4%), influenza (2.7%), lipodystrophy (5.4%), nausea (10.8%), pneumonia (5.4%), pruritus (3.4%), rash (3.4%), sinusitis (2.7%) and vomiting (7.4%). Invirase is not a cure for HIV infection or AIDS. Invirase does not prevent the transmission of HIV. Kaletra® is a registered trademark of Abbott Laboratories Truvada® is a registered trademark of Gilead Sciences, Inc. SOURCE: Hoffmann-La Roche Inc.

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