 |
|
|
| |
Final Gemini Study Results Confirm Boosted Invirase Was as Effective as Kaletra While Providing an Improved Triglyceride Profile for HIV Patients (press release from Roche)
|
| |
| |
-- 48-week results from head-to-head trial between boosted Invirase and boosted lopinavir presented for first time --
Press release from Roche
Nutley, NJ - October 25, 2007 - Final 48-week results from an international head-to-head trial, presented today at the 11th European AIDS Conference (EACS), Madrid, demonstrated that treatment-naive HIV patients treated with the protease inhibitor Invirase® 500mg tablets (saquinavir mesylate), boosted with ritonavir, achieved similar levels of viral suppression and increases in CD4 cells compared to those treated with Kaletra® (lopinavir/ritonavir), a commonly used protease inhibitor. Furthermore, fewer patients treated with Invirase developed elevated triglyceride levels.
"We urgently need HIV treatment options with more favorable lipid profiles, and this is why I welcome the results from the Gemini study," said Professor Sharon Walmsley, Associate Professor of Medicine in the Division of Infectious Diseases, University of Toronto, Canada, and lead investigator on the Gemini study. "These data are of considerable importance because they confirm that Invirase offers treatment-naïve patients an effective treatment to control the virus with significantly smaller increases in triglyceride levels than lopinavir, the most commonly prescribed PI."
Current treatment guidelines for highly active antiretroviral therapy (HAART) include a boosted protease inhibitor (PI/r) as an option for first-line treatment of HIV-infected patients. However, all PI-based regimens can be associated with varying degrees of lipid abnormalities, potentially increasing the risk of developing metabolic syndrome and long-term risk of cerebrovascular and cardiovascular disease. As people with HIV are living for longer due to advances in treatment, it is especially important for trials to explore, and for physicians to consider, the lipid profiles of the various treatment options.
Gemini: Summary of 48-Week Results
These highly anticipated findings are from the final, 48-week analysis of all 337 patients in the Gemini study. The data show that boosted Invirase 500 was not inferior to lopinavir/r, with 64.7 percent and 63.5 percent of patients treated with Invirase/r and lopinavir/r, respectively, achieving undetectable HIV (less than 50 copies per mL of blood. A similar number of patients in both groups (approximately 73 percent) achieved undetectable HIV of less than 400 copies per mL of blood. Furthermore, the rate and extent of increases in CD4 counts were comparable in both groups, with a median increase from baseline of 178 for the Invirase/r-treated patients and 204 for lopinavir/r patients. Finally, the results demonstrate that there was no statistically significant difference in the number of virological failures between the two treatment groups. Adverse events were reported with similar frequency in both study arms.
At 48 weeks, patients treated with Invirase/r showed a lower median increase in their total triglycerides (TG) than patients treated with lopinavir/r (increase of 14 versus 55 mg/dL for TG). In addition, the number of Invirase/r-treated patients who experienced an increase in their lipid levels above those recommended by National Cholesterol Education Program (NCEP) guidelines, as measured by total cholesterol and triglyceride levels, was numerically lower than those treated with lopinavir/r. In the Invirase/r group, the proportion of patients with total cholesterol levels above those recommended in guidelines at week 48 was 31 percent vs. 39 percent for the lopinavir/r group; in TG levels, one percent vs. nine percent; and for LDL levels, 34 vs. 24 percent.
About the Gemini Study
The Gemini study is a Phase IIIb multi-center, randomized open-label, 48 week study, designed to evaluate the efficacy and safety of Invirase 500/r versus lopinavir/r. These treatments are given at their approved twice-daily dosages in combination with two nucleoside reverse transcriptase inhibitors (NRTIs; emtricitabine/tenofovir (Truvada), once daily) in treatment naïve adults. Gemini enrolled 337 patients from Canada, France, Puerto Rico, Thailand and the USA. Of note, the baseline characteristics of patients enrolled in the Gemini study indicated they had more advanced disease compared with patients in several recently published trials, such as KLEAN and ARTEMIS. The primary endpoint of the trial was the number of patients with an HIV-1 RNA viral load of less than 50 copies per mL of blood at week 48. Secondary endpoints were time course of virologic suppression, time course of CD4 cell increase, and safety as assessed by clinical and laboratory adverse events, serious adverse events and deaths.
About Invirase
Invirase, originally approved by the FDA in 1995, was the first protease inhibitor on the market. Its introduction represented a major milestone in the treatment of HIV/AIDS. In December 2003, the FDA approved Invirase for use in boosted dosing regimens with ritonavir (1000 mg Invirase/100 mg ritonavir bid). Co-administering Invirase with ritonavir enhances therapeutic blood levels of the drug ("boosting") and enables simplified dosing.
The Invirase 500 mg formulation received approval from the US Food and Drug Administration (FDA) in December 2004 and from the European Commission in May 2005. The new formulation significantly simplifies the Invirase dosing regimen by reducing the daily tablet count by more than half, from five tablets twice-daily to two tablets twice-daily.
More 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.
About Roche
Hoffmann-La Roche Inc. (Roche), based in Nutley, N.J., is the U.S. pharmaceuticals headquarters of the Roche Group, one of the world's leading research-oriented healthcare groups with core businesses in pharmaceuticals and diagnostics. For more than 100 years in the U.S., Roche has been committed to developing innovative products and services that address prevention, diagnosis and treatment of diseases, thus enhancing people's health and quality of life. An employer of choice, in 2007 Roche was named Top Company of the Year by Med Ad News and one of the Top 20 Employers (Science magazine). In 2006, Roche was ranked the No. 1 Company to Sell For (Selling Power), and one of AARP's Top Companies for Older Workers, and in 2005, Roche was named one of Fortune magazine's Best Companies to Work For in America. For additional information about the U.S. pharmaceuticals business, visit our websites: http://www.rocheusa.com or www.roche.us.
|
| |
|
|
|
|
|
