Value through Innovation02 September 2014
27 July 2011

Viramune® (nevirapine) prolonged-release once-daily formulation for the treatment of HIV-1 infection receives CHMP recommendation for approval

Ingelheim, Germany, 27th July 2011 – Boehringer Ingelheim announced today that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a Positive Opinion recommending the approval of once-daily Viramune® (nevirapine) prolonged-release in all member states of the European Union.1 The CHMP recommendation states that the new prolonged-release tablet is indicated in combination with other antiretroviral medications for the treatment of HIV-1 infection.

The CHMP recommendation — which includes the once-daily, one tablet 400 mg strength for adults and adolescents and the once-daily 50 mg and 100 mg strengths for children — follows clinical trial results confirming the significant therapeutic benefits of nevirapine when administered in a convenient once-a-day formulation.2,3

In the U.S.A., the Viramune® once-daily, one tablet 400 mg formulation was approved by the Food and Drug Administration (FDA) earlier this year.

In clinical trials, the antiviral efficacy of the new once-daily Viramune® prolonged-release 400mg tablet, was shown to be non-inferior to the twice-daily immediate-release 200mg tablet,2,3 with a safety and tolerability profile comparable to nevirapine immediate-release first approved in 1996.

Dr. Keikawus Arastéh, Director of Internal Medicine at Vivantes Auguste-Viktoria-Klinikum, Berlin, Germany

Dr. Keikawus Arastéh

"Switching therapies can improve treatment adherence, which is often key to treatment success. With nevirapine prolonged-release, physicians and their patients can benefit from a simplified, once-daily treatment regimen while still maintaining the high level of efficacy, comparable tolerability, and the favourable lipid profile inherent to the nevirapine immediate release formulation," commented Dr. Keikawus Arastéh, Director of Internal Medicine at Vivantes Auguste-Viktoria-Klinikum, Berlin, Germany.

"Data has shown that the prolonged-release treatment option combines the trusted clinical benefits of nevirapine with the convenience of a single daily dose. Once approved in Europe, Viramune® prolonged-release will allow an easy switch for patients currently taking Viramune® twice-daily, and enable patients to be treated with a regimen that fits in with today’s prescribing trends," added Professor Klaus Dugi, MD, Corporate Senior Vice President Medicine at Boehringer Ingelheim Headquarters

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 Viramune®
Viramune® (nevirapine) is a product of original research done at Boehringer Ingelheim. Nevirapine was the first member of the non-nucleoside reverse transcriptase inhibitor (NNRTI) class of anti-HIV drugs and is indicated for the treatment of HIV-1 infection in combination with other antiretroviral agents. This indication is based on a principal clinical trial that demonstrated prolonged suppression of HIV-RNA and several smaller supportive studies. Studies have also shown that patients switching to nevirapine from a PI-based regimen demonstrate an improved lipid profile while maintaining viral suppression. The clinically most important adverse events associated with nevirapine are rash and hepatic events, which have included fatal cases. The greatest risk of severe rash and hepatic events occurs in the first six weeks of therapy. It is essential that patients be monitored for these reactions at all times, and intensively during the first few months of therapy. Nevirapine should be discontinued and not restarted following severe hepatic, skin or hypersensitivity reactions.

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 nevirapine 400 mg compared to twice-daily nevirapine 200 mg. A total of 1,011 adult patients were randomized to receive either nevirapine prolonged-release or nevirapine immediate-release after a 14-day lead-in period with nevirapine immediate-release for all patients. All patients also received a nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) backbone of Truvada®.*

Results after 48 weeks indicated that of the patients who received nevirapine prolonged-release in the study, 81 percent (404/505) vs. 76 percent (379/506) of patients taking nevirapine immediate-release (200 mg) achieved the study endpoint of viral load <50 copies/mL in the week 48 + 4 window according to the primary endpoint using the Time to Loss of Virologic Response (TLOVR) algorithm. This demonstrated non-inferiority of nevirapine prolonged-release to nevirapine immediate-release. In patients with an HIV-RNA >100,000 copies/mL at baseline, the response rate was 73 percent for nevirapine prolonged-release vs. 71 percent for nevirapine immediate-release. In patients with baseline HIV-RNA≤100,000 copies/mL, the response rate was 85 percent for patients taking nevirapine prolonged-release compared to 79 percent for patients taking nevirapine immediate-release.

VERxVE results also showed that nevirapine prolonged-release had a safety and tolerability profile comparable to nevirapine immediate-release in treatment-naïve patients. After the lead-in period, the incidence of any hepatic event was six percent for adult patients taking nevirapine prolonged-release and nine percent for adult patients taking nevirapine immediate-release. The rate of symptomatic hepatic events was comparable in adult patients taking nevirapine prolonged-release to those patients taking nevirapine immediate-release (two percent vs. three percent).

About the TRANxITION Study

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

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

Safety Information
The most common side effect of nevirapine is rash, which can be severe or life-threatening. The most serious adverse reactions associated with nevirapine 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 145 affiliates and more than 42,000 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.

As a central element of its culture, Boehringer Ingelheim pledges to act socially responsible. Involvement in social projects, caring for employees and their families, and providing equal opportunities for all employees form the foundation of the global operations. Mutual cooperation and respect, as well as environmental protection and sustainability are intrinsic factors in all of Boehringer Ingelheim’s endeavors.

In 2010, Boehringer Ingelheim posted net sales of about 12.6 billion euro while spending almost 24% of net sales in its largest business segment Prescription Medicines on research and development.

References
1European Medicines Agency
2Gathe J et al. Efficacy and safety of nevirapine extended- release once daily versus nevirapine immediate-release twice-daily in treatment-naïve HIV-1 infected patients. Antiviral Therapy 2011;16 (epub ahead of print)
3Arastéh 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 QD. 50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), Boston, MA, USA, September 12-15, 2010: Poster: 207

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

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