European Commission approves statement on lipid improvement for Viramune® label

Boehringer IngelheimBoehringer Ingelheim announced that the European Commission has approved an update of the Summary of Product Characteristics (SmPC) for Viramune® (nevirapine) in the treatment of patients with HIV. The decision followed a positive recommendation by the Committee for Medical Products for Human Use (CHMP), the scientific committee of the European Medicines Agency (EMEA) who reviewed the clinical evidence and approved a statement in the SmPC recognising the positive effect of nevirapine on the lipid profile of HIV infected patients.

The SmPC has been updated to reflect clinical studies demonstrating that nevirapine has been associated with an increase in HDL cholesterol and an overall improvement in the total HDL cholesterol ratio: "In clinical studies, Viramune® has been associated with an increase in HDL- cholesterol and an overall improvement in the total to HDL-cholesterol ratio. However, in the absence of specific studies with Viramune® on modifying the cardiovascular risk in HIV infected patients, the clinical impact of these findings is not known. The selection of antiretroviral drugs must be guided primarily by their antiviral efficacy."

A series of studies (1,2,3) demonstrated a favourable impact of Viramune on the lipid profile for up to two years. The NILE (Nevirapine Intensive Lipid Evaluation)(4) study discovered that Viramune® increases the level of high-density lipoprotein cholesterol HDLc by increasing the enzyme Apo A1. HDLc, is also called "good cholesterol" because of its cardioprotective character.

The impact of Viramune® in the combination with Truvada® on the lipid profile of HIV patients has been further assessed in the ARTEN* trial. This head-to-head study closely mirrors modern HIV treatment conditions and compares two regularly prescribed lipid friendly antiretroviral therapies - Viramune® and atzanavir/r, a protease inhibitor boosted with ritonavir. Results are expected to be announced during the International Aids Society Congress in Cape Town, South Africa from 19 - 22 July 2009.

Dr. Manfred Haehl, MD, Senior Vice-President Medicine at Boehringer Ingelheim said, “We are very satisfied that Viramune®'s positive impact on lipids has been recognized by the European Commission. This is particularly important at a time when cardiovascular disease has become an increasing cause of morbidity and mortality in patients with HIV. Physicians treating patients with HIV need to have a range of treatment options available so they can tailor the therapy to the individual patient's need and response. We are further exploring Viramune® effect on lipid profiles and hope to provide further insights with the upcoming ARTEN study.

About Viramune®
Viramune® is a product of original research done at Boehringer Ingelheim. Viramune® was the first member of the non-nucleoside reverse transcriptase inhibitor (NNRTI) class of anti-HIV drugs. Viramune® is indicated for use in combination with other antiretroviral agents for the treatment of HIV-1 infection. This indication is based on one principal clinical trial that demonstrated prolonged suppression of HIV-RNA and several smaller supportive studies. 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 fatal cases. 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 be 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 138 affiliates in 47 countries and 41,300 employees. Since it was founded in 1885, the independent, family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.

In 2008, Boehringer Ingelheim posted net sales of 11.6 billion euro while spending one fifth of net sales in its largest business segment Prescription Medicines on research and development.

*Atazanavir/Ritonavir on a background of Tenofovir and Emtricitabine (Truvada® a trademark of Gilead Science…) versus Nevirapine

1 van der Valk, M., et al., Nevirapine-containing antiretroviral therapy in HIV-1 infected patients results in an anti-atherogenic lipid profile. Aids, 2001. 15(18): p. 2407-14.
2 van Leth, F., et al., Nevirapine and Efavirenz Elicit Different Changes in Lipid Profiles in Antiretroviral- Therapy-Naive Patients Infected with HIV-1. Plos Med, 2004. 1(1): p. e19.
3 Fisac, C., et al., Metabolic benefits 24 months after replacing a protease inhibitor with abacavir,efavirenz or nevirapine. AIDS, 2005. 19(9): p. 917-25.
4 Sankatsing R, Franssen R, Hassink E et al. Nevirapine increases high density lipoprotein-cholesterol by stimulation of apolipoprotein A-I synthesis. 4th IAS (International AIDS Society) Conf. on HIV Pathogenesis, Treatment and Prevention, Sydney, 22 - 25 Jul 2007, Abstract WEPEB120LB