New data shows HIV therapy tipranavir (Aptivus®) is effective and well tolerated in children

Mexico City, 4 August 2008 – Boehringer Ingelheim today presented new 100 week data at the International AIDS Conference demonstrating Aptivus® (tipranavir) long-term efficacy and safety in treatment-experienced children. Results from this two-year study show that Aptivus® enabled the children to achieve sustained virologic and immunologic responses and was a well-tolerated antiretroviral therapy.

These results build on the positive 48 week data presented in 2006 at the International AIDS Conference in Toronto and submitted to the FDA for the recent approval of the Aptivus® paediatric oral solution and paediatric indication in the United States: Data which is also currently being reviewed by the EMEA for a paediatric and oral solution licences in Europe.

This two-year follow-up data evaluated tipranavir co-administered with low dose ritonavir (Aptivus/r) in 78 treatment-experienced children. Those completing the original 48 week trial were given the choice of continuing their therapy with Aptivus® for an extension of the trial. The continuing analysis confirms the results of the 48 week data and demonstrates the durability of Aptivus®. Over half of younger children in the trial achieved sustained virologic response and the oral solution continued to be well tolerated over the 100 weeks.

Dr. Manfred Haehl, Corporate Senior Vice President Medicine at Boehringer Ingelheim said, “We are pleased that tipranavir showed such a positive efficacy and safety profile in treatment-experienced children who have fewer treatment options than adults and need more therapy choices, including therapies that have been specially formulated to meet their needs.”

The number of children diagnosed with HIV/AIDS is growing. There are approximately 2.1 million children living with HIV worldwide and recent statistics show that another 29,000 will be infected with the disease this year alone.¹ Once a child is infected with HIV, they face a higher chance of developing AIDS unless they can successfully be treated with antiretroviral therapy. Just as with adults, children can become resistant to certain therapies which underscores the need for an increase in treatment options active against drug-resistant HIV.

The data, collected in over 26 sites in Europe, the United States and Latin America, shows that HIV-1 positive children and adolescents receiving tipranavir boosted by ritonavir as part of their combination antiretroviral therapy can achieve sustained virologic and immunologic responses at 100 weeks of therapy: after 100 weeks of treatment, 56% of children between 2 and 6 years achieved a viral load of less than 400 copies per ml, and 48% of this age group saw their viral loads drop to undetectable levels (less than 50 copies per ml).

For the 6 to 12 years old group, 30% achieved an undetectable viral load (less than 50 copies per ml), and for the 12 to 18 years old group, still over 20% achieved an undetectable viral load. The lower rate of undetectable viral loads in older children is due to them being more treatment-experienced and harbouring HIV which has become more drug-resistant than in younger children.

“There are many children and adolescents with HIV who fail to maintain viral suppression of the disease, which speaks to the urgent need for a new generation of therapies designed specifically for this group,” noted lead author of the analysis and Associate Professor of Paediatrics, Dr. Juan Salazar, MD, MPH, Connecticut Children’s Medical Centre, Hartford, CT, USA. “For these treatment-experienced children who have had limited options for maintaining an active and durable treatment regimen, we now have evidence that tipranavir is effective and tolerable.”

Up to 50% of HIV-infected children and adolescents fail to maintain suppression of HIV replication beyond two years of initial treatment, according to some studies,^2,3 and up to 90% of children who fail antiviral therapy carry drug-resistant strains of HIV. These statistics make it critical that new options are made available which are able to suppress HIV in the treatment-experienced paediatric group.

The most common side effect was gastrointestinal effects such as vomiting and diarrhoea, while over 6% of patients experienced Grade 3 liver enzyme rises (ALT). None of the patients experienced Grade 4 ALT elevations, indicating an acceptable hepatoxicity profile.

About Aptivus®
Aptivus® is a non-peptidic protease inhibitor which works by inhibiting the viral protease, an enzyme needed to complete the HIV replication process. Based on available clinical and in-vitro data, Aptivus® is active against most strains of HIV-1 that are resistant to commercially available protease inhibitors. It is approved for combination antiretroviral treatment of HIV-1 infected adults that are highly pre-treated with virus resistant to multiple protease inhibitors.

RESIST I and II –two large-scale clinical studies on Aptivus® involving more than 1,400 patients formed the foundation for granting traditional approval by the FDA and full marketing authorization by the EMEA. The RESIST clinical trial program is one of the largest study programs undertaken with an investigational antiretroviral agent in patients previously treated with multiple combinations of antiretroviral drug regimens.

Aptivus® can be combined with new agents with novel mechanisms of action (e.g. integrase inhibitors and CCR-5 antagonists) without dose adjustment to build efficacious and durable treatment regimens. Such a benefit has been clearly demonstrated by favourable results with the concomitant use of APTIVUS in combination with new drug classes.^4,5

The most commonly reported side effects of at least moderate intensity in patients enrolled in the RESIST studies taking Aptivus® are gastrointestinal, including diarrhoea, nausea, vomiting and abdominal pain. Fever, fatigue, headache, bronchitis, depression and rash also occurred. Elevated transaminase, cholesterol and triglycerides were more frequent in the Aptivus®/r arm than in the ritonavir boosted comparator group but only in a minority of cases treatment discontinuation was necessary.

Aptivus® boosted with low-dose ritonavir has been associated with reports of hepatic adverse events, which have included some fatalities. These have generally occurred in patients with advanced HIV disease taking multiple concomitant medications. Extra vigilance is warranted in patients with chronic hepatitis B or hepatitis C co-infection, as these patients have an increased risk of liver toxicity. The most common moderate to severe laboratory abnormalities were elevated liver enzymes and elevated lipid levels. Most laboratory abnormalities were asymptomatic and most patients were successfully treated without discontinuation.

Aptivus®-containing HAART regimens have been associated with reports of both fatal and non-fatal intracranial haemorrhage (ICH) in some highly treatment-experienced patients. Caution should be used when prescribing Aptivus®/r in patients who may be at risk of increased bleeding or who are receiving medications known to increase the risk of bleeding.

Aptivus® does not cure HIV infection/AIDS or prevent the transmission of HIV to others. Patients may continue to develop opportunistic infections and other complications associated with HIV disease.

Aptivus® received U.S. marketing authorization by the U.S. Food and Drug Administration (FDA) and was launched in the Unites States in June 2005. On October 4th, 2007, the FDA granted traditional approval for Aptivus®, and in April 2008 the EMEA granted full marketing authorisation for Aptivus® in Europe. Additional marketing authorizations from different countries have been received or are expected.

Aptivus® OS (oral solution) received U.S. marketing authorization for use in treatment experienced children and adolescents by the U.S. Food and Drug Administration (FDA) on 24 June 2008.

About Boehringer Ingelheim HIV Clinical Trials
Boehringer Ingelheim is actively conducting clinical trial programs to further evaluate Aptivus® and the non-nucleoside-reverse transcriptase inhibitor (NNRTI) Viramune® for the treatment of HIV-1 infection.

The Viramune® clinical trial program includes the ArTEN trial, which aims to compare the efficacy and safety of Viramune dosed once or twice daily versus atazanavir boosted with ritonavir in HIV-positive antiretroviral-naïve patients. The ArTEN trial will enrol 561 HIV-positive patients who have yet to be treated with antiretrovirals.

About Boehringer Ingelheim
Boehringer Ingelheim is committed to the research and development of novel antiretroviral agents. Apart from Aptivus® (tipranavir), Viramune® (nevirapine) 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 on the market. The company is involved in basic research in that area and is committed to improving HIV therapy by providing physicians and patients with innovative antiretroviral treatment options.

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.