Study Shows Once-Daily, Extended-Release Formulation of Nevirapine was not Inferior to Twice-Daily VIRAMUNE in Treatment-Naive HIV-1 Infected Patients

RIDGEFIELD, Conn., July 22 /PRNewswire/ -- New data were presented today at the 18th International AIDS Conference from the VERxVE study that show an investigational, once-daily extended-release (400 mg QD) formulation of nevirapine was non-inferior to twice-daily immediate release Viramune® (nevirapine) tablets (200 mg BID), both in combination with Truvada® (tenofovir and emtricitabine) tablets in treatment-naive HIV-1 infected patients through 48 weeks.

"We are pleased to see that the VERxVE study met its primary endpoint, and provided data on the efficacy and safety of an investigational, extended-release formulation of nevirapine," said Peter Piliero, M.D., executive director, Medical Affairs, Boehringer Ingelheim Pharmaceuticals, Inc.  

The investigational, extended-release formulation of nevirapine had a similar safety profile to immediate release VIRAMUNE in the trial.

VERxVE was a randomized, double-blind, double-dummy, parallel group, active controlled trial that evaluated the antiviral efficacy of the extended-release formulation of nevirapine  in comparison to immediate release VIRAMUNE, both in combination with Truvada®, in treatment-naive HIV-1 infected patients. A total of 1,068 patients enrolled in VERxVE and 1,011 patients were randomized and received either the extended-release (400 mg QD) formulation of nevirapine or immediate release VIRAMUNE (200 mg BID) after a required 14-day lead-in period with immediate release VIRAMUNE for all patients. All patients also received a NRTI backbone of Truvada®.

The study's primary endpoint was confirmed virologic response through 48 weeks of treatment, with response defined as a viral load of <50 copies/mL measured on two consecutive occasions at least two weeks apart prior to or at week 48 and without subsequent rebound or change of therapy prior to or at week 48. VERxVE follow-up is currently planned to continue for a total of 144 weeks.  

Boehringer Ingelheim Pharmaceuticals, Inc. is working with regulatory authorities to make the extended-release formulation of nevirapine available.

VERxVE Results

Of the patients who received the extended-release formulation of nevirapine (400 mg QD) in the study, 81 percent (409/505) achieved the study's primary endpoint of viral load of < 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 percent (384/506) of patients taking immediate release VIRAMUNE (200 mg BID) (95 percent CI -0.11 to +9.96).

In patients with a HIV-RNA >100,000 copies/mL at baseline, the response rate was 73 percent for the extended-release formulation of nevirapine vs. 71 percent for immediate release Viramune® (nevirapine) tablets. In patients with baseline HIV-RNA ≤ 100,000 copies/mL, the response rate was 79 percent for patients taking immediate release VIRAMUNE compared to 86 percent for patients taking the extended-release formulation of nevirapine.

In the VERxVE trial, a double-blind, double-dummy study, adverse events seen with the extended-release formulation of nevirapine were similar to those seen with the FDA-approved immediate release VIRAMUNE.  The most common adverse events for the extended-release formulation of nevirapine were nasopharyngitis (inflammation of the nasal passages), diarrhea, upper respiratory tract infection, rash and headache. No new or unexpected safety issues were identified for immediate release VIRAMUNE. The number of discontinuations due to adverse events in the extended-release formulation of the nevirapine study arm was 32 (6.3 percent) vs. 45 (8.9 percent) in the immediate release VIRAMUNE study arm.  The rate of symptomatic hepatic events was 1.6 percent in patients taking the extended-release formulation of nevirapine compared to 2.8 percent in those taking immediate release VIRAMUNE.  The rate of rash events in the study was 8.3 percent vs. 8.7 percent respectively for the extended-release formulation of nevirapine and immediate release VIRAMUNE.  The safety data presented in this paragraph showed no statistically significant difference between arms.

Three cases of Stevens-Johnson syndrome occurred with the use of immediate release VIRAMUNE during the two week lead-in dose while another two cases occurred after randomization, also in the immediate release arm. There was no occurrence of Stevens-Johnson syndrome in patients randomized to the extended-release formulation of nevirapine.  The VERxVE data demonstrates a similar safety profile between the two arms, and therefore, the absence of Stevens-Johnson syndrome with the extended-release formulation of nevirapine in this study does not mean that it cannot occur.

Data captured during the 14-day lead-in period (when all patients received immediate release VIRAMUNE (200 mg QD) before being randomized to the extended-release formulation of nevirapine or immediate release VIRAMUNE arms of the study) are not included in the VERxVE analysis.  The immediate release formulation of VIRAMUNE (200 mg BID) is not otherwise approved for once-daily dosing, as the safety and efficacy of once-daily dosing has not been established.

Important Safety Information for immediate release Viramune® (nevirapine) tablets

VIRAMUNE is indicated for use in combination with other antiretroviral agents for the treatment of HIV infection.

VIRAMUNE does not cure HIV or AIDS, and has not been shown to reduce the risk of passing HIV to others through sexual contact or blood contamination.

VIRAMUNE can cause severe liver disease and skin reactions that can cause death. These reactions occur most often during the first 18 weeks of treatment, but can occur later. Ask your healthcare provider about how to recognize symptoms of skin and liver problems.

Stop taking Viramune® (nevirapine) tablets if you have any of these reactions. Do not restart VIRAMUNE if you experience any of these reactions. Call your healthcare provider immediately if you have any of these reactions.

VIRAMUNE is only for people diagnosed with HIV. If you have not been diagnosed as HIV positive, then do not take VIRAMUNE.

Any patient can experience liver problems with VIRAMUNE, but women and patients who have higher CD4 counts when they begin VIRAMUNE treatment have a greater risk. If you are a woman with CD4+ >250 cells/mm(3), or a man with CD4+ >400 cells/mm(3), you should not begin taking VIRAMUNE unless you and your doctor have decided that the benefit of doing so outweighs the risk. Women, including pregnant women, with CD4+ cell counts >250 cells/mm3 are at the greatest risk.

Do not take VIRAMUNE if you have severe liver problems.

The dose of VIRAMUNE for adults is one 200-mg tablet daily for the first 14 days, followed by one 200-mg tablet twice daily. VIRAMUNE is always taken with other anti-HIV medications. The 14-day lead-in period is important because it can help reduce your chances of getting a potentially serious skin rash. If you have a skin rash during the first 14 days, immediately contact your doctor and do not increase your VIRAMUNE dose to twice a day. The total duration of the once daily lead-in dosing period should not exceed 28 days, at which point an alternative regimen may need to be started.

Other side effects that patients have experienced include nausea, fatigue, fever, headache, vomiting, diarrhea, abdominal pain, and myalgia. Changes in body fat may occur in patients receiving antiretroviral therapy. Immune reconstitution syndrome has been reported in patients treated with combination ARV therapy.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

Please see full Prescribing Information, including boxed WARNING, and Medication Guide for VIRAMUNE at www.viramune.com.

About Boehringer Ingelheim Pharmaceuticals, Inc.

Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation (Ridgefield, CT) and a member of the Boehringer Ingelheim group of companies.

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 US $17.7 billion (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 http://us.boehringer-ingelheim.com and follow us on Twitter at http://twitter.com/boehringerus. 

*Truvada is a registered trademark of Gilead Sciences, Inc.

SOURCE Boehringer Ingelheim Pharmaceuticals, Inc.