Value through Innovation22 July 2014
31 March 2011

U.S. FDA approves once-daily Viramune® XR™ tablet for use in combination with other antiretroviral agents for treatment of HIV-1 infection in adults

Once-daily, extended-release Viramune® can help reduce pill burden for patients

Ingelheim, Germany, 31 March 2011 - Boehringer Ingelheim announced today that the U.S. Food and Drug Administration (FDA) has approved Viramune® XR™ (nevirapine) extended-release tablets — a one-pill, once-daily (400 mg) formulation of nevirapine — for use in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults.

“With the approval of once-daily Viramune® XR™, patients in the U.S.A. now have the benefit of a new HIV treatment option for use in combination with their other HIV medications,” said Joseph Gathe, Jr., M.D., clinical instructor, Department of Internal Medicine, Baylor College of Medicine and lead investigator of the VERxVE clinical trial. “Physicians in the U.S.A. can now switch their current Viramune® patients to a once-daily product with demonstrated comparable safety and efficacy.”

“With the approval of once-daily Viramune®XR™, patients in the U.S.A. now have the benefit of a new HIV treatment option for use in combination with their other HIV medications”

The approval of Viramune® XR™ was based on data from the Phase III VERxVE1 study, which demonstrated that Viramune® XR™ achieved a virologic response non-inferior to twice-daily immediate-release Viramune® (200 mg) through 48 weeks, both used in combination with Truvada®, in treatment-naïve HIV-1 infected adult patients. Results also showed that in treatment-naïve patients, Viramune® XR™ had a safety and tolerability profile comparable to immediate-release Viramune® which was first approved in 1996.

“Pill burden is an important consideration for patients in need of HIV therapy. Boehringer Ingelheim is committed to not only improving HIV therapy by providing physicians and patients with innovative antiretroviral medicines like Viramune®, but also by providing therapies that may improve treatment adherence,” said Professor Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim. “For patients in the U.S.A. switching to once-daily Viramune® extended-release, the new tablet provides a treatment option with less frequent dosing that will help to reduce the patient’s pill burden.”

The results of the supportive open-label study TRANxITION2 showed that patients can be safely switched from the current available formulation of Viramune® to Viramune® XR™.

The recommended dose for Viramune® XR™ is one 400 mg tablet taken once daily, with or without food, in combination with other antiretroviral agents. For adult patients switching from immediate-release Viramune® to Viramune® XR™, there is no lead-in dosing.

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Notes to Editor:

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.

About the VERxVE Study
VERxVE is a randomized, double-blind, double-dummy, parallel group, active controlled, multinational trial conducted to evaluate the antiviral efficacy and safety of once-daily Viramune® XR™ (400 mg) compared to twice-daily, immediate-release Viramune® (200 mg). A total of 1,011 adult patients were randomized to receive either Viramune® XR™ or immediate-release Viramune® after a 14-day lead-in period with immediate-release Viramune® for all patients. All patients also received a nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) backbone of Truvada®.

Of the patients who received Viramune® XR™ in the study, 80 percent (404/505) vs. 75 percent (379/506) of patients taking immediate-release Viramune® (200 mg) achieved the study endpoint of viral load <50 copies/mL in the week 48 + 4 window, using the last viral load measurement if multiple measurements were taken in the window (Snapshot analysis). This demonstrated non-inferiority of Viramune® XR™ to immediate-release Viramune®. In patients with an HIV-RNA>100,000 copies/mL at baseline, the response rate was 73 percent for Viramune® XR™ vs. 71 percent for immediate-release Viramune®, using the Time to Loss of Virologic Response (TLOVR) algorithm. In patients with baseline HIV-RNA≤100,000 copies/mL, the response rate was 86 percent for patients taking Viramune® XR™ compared to 79 percent for patients taking immediate-release Viramune®.

VERxVE results also showed that Viramune® XR™ had a safety and tolerability profile comparable to immediate-release Viramune® in treatment-naïve patients. After the lead-in period, the incidence of any hepatic event was six percent for adult patients taking Viramune® XR™ and nine percent for adult patients taking immediate-release Viramune®. The rate of symptomatic hepatic events was comparable in adult patients taking Viramune® XR™ to those taking Viramune® (two percent vs. three percent). Five cases of Stevens-Johnson syndrome were reported in the trial, all of which occurred within the first 30 days of nevirapine treatment.

About the TRANxITION Study
The TRANxITION study examined the efficacy and safety of switching virologically-suppressed patients (viral load < 50 copies/ml) from Viramune® immediate release 200mg twice daily to Viramune® XR™ 400mg once daily.

TRANxITION is an open-label, parallel group, non-inferiority, randomised study (2:1 randomisation Viramune® XR™ : Viramune® immediate release). Adult HIV-1 patients receiving Viramune® immediate release plus fixed-dose NRTI combinations with undetectable viral load were enrolled. The primary endpoint was continued virologic suppression with VL <50 copies/mL through Week 24. In the study, 443 patients from the USA and Europe were treated; 295 switched to Viramune® XR™ and 148 continued onViramune®. Virologic suppression was observed in 93.6 percent (276/295) with Viramune® XR™ and in 92.6 percent (137/148) with Viramune® immediate-release at 24 weeks of follow-up. Non-inferiority (adjusted margin of -10 percent) of Viramune® XR™ to Viramune® immediate release was robust. The rate of severe adverse events was low and comparable between both treatment groups (3.7 percent and 4.1 percent with the XR and immediate formulations respectively). The study supports the switch from Viramune® immediate release twice daily to Viramune® XR™ once-daily in patients who are virologically suppressed.

Safety Information
The most common side effect of immediate-release Viramune® and Viramune® XR™ is rash, which can be severe or life-threatening. The most serious adverse reactions associated with immediate-release Viramune® and Viramune® XR™ are hepatitis, hepatic failure, Stevens-Johnson syndrome, toxic epidermal necrolysis, and hypersensitivity reactions. Hepatitis/hepatic failure may be isolated or associated with signs of hypersensitivity, which may include severe rash or rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis (pink eye), facial edema, eosinophilia (an abnormally high number of eosinophils in the blood), granulocytopenia (an abnormally low concentration of granulocytes in the blood), lymphadenopathy (swelling/enlargement of the lymph nodes), or renal dysfunction.

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.

(Truvada® is a registered trademark of Gilead Sciences, Inc.)

References
1Gathe 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.
2Arastéh K et al. 24 Wk Efficacy and Safety of Transitioning Virologically Stable HIV-1 Patients from IR Nevirapine 200 mg BID to Nevirapine XR 400 mg Q. 50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), Boston, MA, USA, September 12-15, 2010: Poster: 207.

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