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VERxVE study demonstrates efficacy and safety of 400mg once daily nevirapine (Viramune) extended release (NVP XR) formulation - BI press release
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Ingelheim/Germany and Vienna/Austria, 22 July 2010 - Results from the VERxVE study presented today at the 18th International AIDS Society (IAS) conference in Vienna, Austria, show that once daily nevirapine extended release (XR) formulation (400mg QD) Viramune is non-inferior to the currently used twice daily immediate release (200mg BID) Viramune (IR) through 48 weeks.
VERxVE is a pivotal trial that compared the frequently prescribed lipid-friendly* antiretroviral Viramune IR with once daily nevirapine (Viramune XR.) At week 48, virologic response was 81% (409/505) for nevirapine extended release formulation compared with 75.9% (384/506) for Viramune IR. There was an adjusted difference of 4.9% in favour of nevirapine extended release formulation (95% CI: -0.1%-10.0%), demonstrating non-inferiority.
The 400mg QD nevirapine extended release formulation (Viramune XR) demonstrated adequate trough drug exposure through 48 weeks, and efficacy was consistent across gender, baseline viral load and country of origin. Both formulations demonstrated a similar adverse event profile and no new side effects were identified.
"Like the ARTEN trial, the VERxVE trial demonstrates the efficacy and safety of the combination of Viramune with Truvada," said Joseph Gathe, Therapeutic Concepts, Houston, Texas, USA and lead investigator of the VERxVE study. "It confirms that this once daily combination is very efficacious and significantly increases HDL-c, the so-called good cholesterol."
In the VERxVE study, 1,011 patients were randomized and treated. Median baseline viral load was 4.7 log10 copies/mL for both arms (XR and IR). Demographics, other disease characteristics and length of exposure to study drug were also similar between arms.
Viramune increased mean absolute HDL-c from baseline (13.4 mg/dL for Viramune IR and 10 mg/dL for nevirapine extended release formulation (Viramune XR)). Mean increases in LDL cholesterol were 10 mg/dL in each of the treatment groups. The total mean cholesterol over HDL-c ratio decreased in both treatment groups by 14% in the IR group and 12% in the XR group.
"We are very pleased with the VERxVE results," said Prof. Klaus Dugi, Corporate Senior Vice President Medicine at Boehringer Ingelheim, "as they confirm Viramune as a potent choice in antiretroviral therapy. We are confident that the extended release formulation, once approved, will enable HIV patients and their physicians to choose an effective, tolerable and durable treatment option with a favourable lipid profile. This development is particularly important as it will give patients the convenience of a once daily antiretroviral drug that does not carry food or drink restrictions."
The adverse event (AE) profile of both formulations was similar: investigator defined drug-related AEs were observed in 19.8% of nevirapine extended release formulation (Viramune XR), vs 24.3% for Viramune IR. The overall rate of symptomatic hepatic events was 1.6% for the nevirapine extended release formulation (Viramune XR) vs. 2.8% for Viramune IR), while the rate of rash was 8.3% vs 8.8%, respectively, for nevirapine extended release formulation (Viramune XR) and Viramune IR.
Boehringer Ingelheim is working with regulatory authorities worldwide to make the nevirapine XR formulation available as soon as possible.
About VERxVE
An international, randomized, double blind, double dummy, parallel group trial to evaluate the antiviral efficacy of 400mg QD nevirapine extended release formulation compared with 200mg BID nevirapine (immediate release). Both nevirapine formulations were used in combination with Truvada.
The study enrolled 1,068 participants from the USA, Europe, Africa and Australia, all of whom were antiretroviral-naïve HIV-1 infected adults (>18 years). Entry criteria included baseline viral load >1,000 copies/mL and CD4 count <400 cells/mm3 for males and <250 cells/mm3 for females. All participants received a 14-day lead-in dose of 200mg Viramune once daily and 1,011 were randomized to receive either 400mg QD (extended release) or 200mg BID (immediate release).
The primary objective was to evaluate the efficacy of 400mg QD nevirapine extended release (NVP XR) formulation versus 200 mg BID nevirapine immediate release (NVP IR) in antiretroviral therapy naïve HIV-1 infected patients after 48 weeks of treatment. Secondary objectives are to evaluate the safety and pharmacokinetics of NVP XR and NVP IR. The VERXVE study has an extension through 144 weeks.
VERxVE: key findings
Once daily nevirapine extended release (400 mg QD) was non-inferior to twice daily immediate release Viramune (200 mg BID) through 48 weeks, both in combination with Truvada® in treatment-naïve HIV-1 infected patients.
Of the patients who received nevirapine XR (400 mg QD) in the study, 81% (409/505) achieved undetectable viral load (< 50 copies/mL) on two occasions by week 48 and without subsequent rebound or change of antiretroviral therapy prior to or at week 48, vs. 76% (384/506) of patients taking immediate release Viramune® (200 mg BID).
In patients with baseline HIV-RNA ≤ 100,000 copies/mL, the response rate was 86% for patients taking nevirapine XR vs 79% for Viramune IR. In patients with HIV-RNA >100,000 copies/mL at baseline, the response rate was 73% for nevirapine XR vs. 71% for Viramune IR.
The safety profile of nevirapine XR (400 mg QD) is similar to the Viramune IR (200 mg BID). There were fewer discontinuations due to adverse events in the nevirapine XR study arm (n=32, 6.3%) vs. Viramune IR study arm (n=45, 8.9%).
The most common adverse events for nevirapine XR were nasopharyngitis, diarrhea, upper respiratory tract infection, rash and headache.
· The overall rate of symptomatic hepatic events was lower in patients taking nevirapine XR (1.6% vs. 2.8%). The rate of rash events was similar between nevirapine XR and Viramune IR (8.3% vs. 8.7%).
About Viramune
Viramune is a product of original research carried out at Boehringer Ingelheim. Viramune was the first anti-HIV drug in the non-nucleoside reverse transcriptase inhibitor (NNRTI) class. Viramune® is indicated for use in combination with other antiretroviral agents for the treatment of HIV-1 infection.
Studies have also shown that patients switching to Viramune from a PI-based regimen demonstrate an improved lipid profile while maintaining viral suppression. The most clinically important adverse events associated with Viramune are rash and hepatic events, which have included fatalities. Any patient can experience hepatic events; however, female gender and higher CD4+ cell counts at initiation of therapy place patients at greater risk. Women with CD4+ cell counts >250 cells/mm3 are at the greatest risk. Viramune should not be initiated in adult females with CD4+ cell counts greater than 250 cells/mm3 or in adult males with CD4+ cell counts greater than 400 cells/mm3 unless the benefit outweighs the risk. The greatest risk of severe rash and hepatic events occurs in the first six weeks of therapy. It is essential that patients are monitored for these reactions at all times, and intensively during the first few months of therapy. Viramune should be discontinued and not restarted following severe hepatic, skin or hypersensitivity reactions.
About Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 142 affiliates in 50 countries and more than 41,500 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.
In 2009, Boehringer Ingelheim posted net sales of 12.7 billion euro while spending 21% of net sales in its largest business segment Prescription Medicines on research and development.
For more information please visit www.boehringer-ingelheim.com
Please be advised
This release is from Boehringer Ingelheim Corporate Headquarters in Germany. Please be aware that there may be national differences between countries regarding specific medical information, including licensed uses. Please take account of this when referring to the information provided in this document. This press release is not intended for distribution within the U.S.A.
Contact
Ute E. Schmidt
Corporate Division Communications
Boehringer Ingelheim GmbH
55216 Ingelheim/Germany
Phone: + 49 - 6132 - 77 97296
Fax: + 49 - 6132 - 72 6601
E-mail: press@boehringer-ingelheim.com
Twitter: www.twitter.com/boehringer
Reference:
Gathe J et al. Comparison of 48 week efficacy and safety of 400mg QD nevirapine extended release formulation (Viramune XR) versus 200mg BID nevirapine immediate release formulation (Viramune IR) in combination with Truvada in antiretroviral (ARV) naïve HIV-1 infected patients (VERxVE). XVIII International AIDS Conference, Vienna, Austria; July 18-23, 2010: oral presentation.
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