Ridgefield, Conn., June 24, 2008 -- Boehringer Ingelheim Pharmaceuticals, Inc. today announced that the U.S. Food and Drug Administration (FDA) granted approval of Aptivus (tipranavir) capsules/oral solution with dosing information for treatment-experienced pediatric patients between the ages of 2-18 infected with HIV-1. The oral solution formulation, which is a new dosage form of Aptivus, was also approved for treatment-experienced adults. The oral solution formulation will be available in the U.S. beginning in mid-September. The FDA granted full (traditional) approval to Aptivus capsules for treatment-experienced adults in October 2007.

"Due to significant advances in HIV therapy and care, many perinatally infected children are growing into young adulthood and beyond. Most of these children have received multiple courses of anti-HIV medications and many have evidence that their HIV strains have developed resistance to the majority of currently approved antiretrovirals. An unmet need remains for pediatric indications and new formulations of antiretroviral therapies," said Dr. Juan Salazar, Associate Professor in Pediatrics, University of Connecticut's Department of Pediatrics, Division of Pediatric Infectious Diseases, and Director of the Pediatric and Youth HIV Program at the Connecticut Children's Medical Center. "This approval is an important development for treatment-experienced children and teenagers who may have limited therapeutic options."

Aptivus Indications and Usage

Aptivus, a protease inhibitor co-administered with ritonavir (Aptivus/r), is indicated for combination antiretroviral treatment of HIV-1 infected patients who are treatment-experienced and infected with HIV-1 strains resistant to more than one protease inhibitor.

This indication is based on analyses of plasma HIV-1 RNA levels in two controlled studies of Aptivus/r of 48 weeks duration in treatment-experienced adults and one open-label 48-week study in pediatric patients age 2 to 18 years. The adult studies were conducted in clinically advanced, 3-class antiretroviral (NRTI, NNRTI, PI) treatment-experienced adults with evidence of HIV-1 replication despite ongoing antiretroviral therapy.

The following points should be considered when initiating therapy with
Aptivus/r:

• The use of Aptivus/r in treatment-naive patients is not recommended.

• The use of other active agents with Aptivus/r is associated with a greater likelihood of treatment response.

• Genotypic or phenotypic testing and/or treatment history should guide the use of Aptivus/r. The number of baseline primary protease inhibitor mutations affects the virologic response to Aptivus/r.

• Use caution when prescribing Aptivus/r to patients with elevated transaminases, hepatitis B or C co-infection or patients with mild hepatic
impairment.

• Liver function tests should be performed at initiation of therapy with Aptivus/r and monitored frequently throughout the duration of treatment.

• The drug-drug interaction potential of Aptivus/r when co-administered with other drugs must be considered prior to and during Aptivus/r use.

• Use caution when prescribing Aptivus/r in patients who may be at risk for increased bleeding or who are receiving medications known to increase the risk of bleeding.

• The risk-benefit of Aptivus/r has not been established in pediatric patients less than 2 years of age.

• There are no study results demonstrating the effect of Aptivus/r on clinical progression of HIV-1.

• Aptivus/r does not cure HIV or help prevent passing HIV to others.

According to Centers for Disease Control and Prevention (CDC) data for 33 states, an estimated 8,545 children and adolescents under the age of 20 were living with HIV/AIDS in the U.S. at the end of 2006.(1) The estimated number of 13 to 19-year-olds living with HIV/AIDS increased by 28 percent from 2003 to 2006.(1)

Aptivus/r has been studied in a total of 135 HIV-1 infected pediatric patients age 2 through 18 years as combination therapy. This study enrolled HIV-1 infected, treatment-experienced pediatric patients (with the exception of 3 treatment-naive patients), with baseline HIV-1 RNA of at least 1,500 copies/mL. One hundred and ten (110) patients were enrolled in a randomized, open-label 48-week clinical trial (study 1182.14) and 25 patients were enrolled in other clinical studies including Expanded Access and Emergency Use Programs.

All patients initially received Aptivus oral solution. Pediatric patients who were 12 or older and received the maximum dose of 500/200 mg twice daily could subsequently change to Aptivus capsules at day 28. The trial primarily compared two doses for safety and tolerability based on adverse events and laboratory findings, and secondarily evaluated pharmacokinetics and virologic and immunologic response and time to treatment failure at 48 weeks.

Based on the results, the recommended pediatric dose of Aptivus for both capsules and oral solution is 14 mg/kg with 6 mg/kg ritonavir, or 375 mg/m2 co-administered with ritonavir 150 mg/m2, taken twice daily. A greater proportion of patients receiving this dose achieved a viral load of less than 400 copies/mL. For children who develop intolerance or toxicity and cannot continue with the higher dose, physicians may consider decreasing the dose to APTIVUS 12 mg/kg with 5 mg/kg ritonavir, or Aptivus 290 mg/m2 co-administered with 115 mg/m2 ritonavir, taken twice daily, provided their virus is not resistant to multiple protease inhibitors.

Prescribers should calculate the appropriate dose of Aptivus for each individual child based on body weight (kg) or body surface area (BSA, m2) and should not exceed the recommended adult dose of Aptivus 500 mg co-administered with ritonavir 200 mg twice daily.

At 48 weeks, 40 percent of patients had a viral load of less than 400 copies/mL. The proportion of patients with viral load less than 400 copies/mL tended to be greater (70 percent) in the youngest group of patients, who had less viral resistance at baseline, compared to the older groups (37 percent and 31 percent). Agents approved by the FDA in the past five months were not included in the trial.

The most frequent adverse reactions in pediatric patients were similar to those in adults. Fever, vomiting, cough, rash, nausea and diarrhea were most frequently reported, and rash was reported more frequently in pediatric patients than in adults. The most frequent treatment-emergent laboratory abnormalities were increases in CPK, ALT and amylase.

Patients taking Aptivus oral solution should be advised not to take supplemental vitamin E greater than a standard multivitamin as Aptivus oral solution contains 116 IU/mL of vitamin E which is higher than the Reference Daily Intake (adults 30 IU, pediatrics approximately 10 IU).

"The approval of a new formulation and the pediatric indication demonstrates Boehringer Ingelheim's commitment to the community and patients with advanced stage HIV," said Dr. Thor Voigt, Senior Vice President, Medicine and Drug Regulatory Affairs, Boehringer Ingelheim Pharmaceuticals, Inc. "Aptivus oral solution provides physicians and patients with an important treatment option in the fight against HIV/AIDS."

Please see full Prescribing Information, including boxed WARNINGS, for Aptivus at www.aptivus.com.