First NNRTI Suspension, VIRAMUNE(R), Now Available for

Use in HIV-Positive Children / European Commission ApprovalAdvances Fight Against Paediatric HIV/AIDS INGELHEIM, Germany (PROTEXT) - Boehringer Ingelheim announcedtoday that it has received approval from the European Commissionto market a paediatric formulation of the AIDS drug VIRAMUNE(R)(nevirapine) to treat infants and children infected with HIV.VIRAMUNE is the first oral suspension belonging to the class ofdrugs called NNRTIs, or non-nucleoside reverse transcriptaseinhibitors, to be approved in the European Union (EU) for use incombination therapy for the treatment of paediatric HIV/AIDS. "VIRAMUNE's paediatric formulation broadens the therapeuticoptions for HIV-positive children, particularly for thosechildren who are in need of new treatment options due tointolerable dosing and side effects or resistance," said John L.Sullivan, MD, Professor of Pediatrics, University ofMassachusetts Medical School, Worcester, and one of the leadinvestigators for the paediatric formulation. "Some of thecurrently available agents are very effective, but tasteterrible; therefore getting kids to swallow such drugs is verydifficult. VIRAMUNE, in comparison, is a pleasant-tasting liquidsuspension administered twice daily. We have found that VIRAMUNEis easy for children to take and is generally well tolerated." According to the December 1998 United Nations Joint Programmeon AIDS (UNAIDS)/World Health Organisation (WHO) report on theglobal AIDS epidemic, over 770,000 children in Europe and CentralAsia under the age of 15 are infected with HIV/AIDS, and youngpeople (aged 15-24) accounted for nearly half of all new HIVinfections in 1998. VIRAMUNE's paediatric suspension marks theseventh agent to be approved to treat HIV in paediatric patientsin the EU. There are currently 12 available agents for adults. "We're pleased that VIRAMUNE's paediatric formulation is nowavailable in Europe," said Professor Rolf Krebs, Vice Chairman ofthe Board of Managing Directors responsible for the DivisionPharma at Boehringer Ingelheim. "Research has shown that Viramuneis a potent and safe agent for treating children and adolescentsinfected with HIV." "Boehringer Ingelheim is committed to the ongoing study ofVIRAMUNE in children and adults, as well as to pursuing othertreatments that could benefit the HIV community," commentedProfessor Krebs. Efficacy and Safety To date, more than 360 children as young as two months oldhave been treated with VIRAMUNE in clinical trials. Some haveremained on therapy for as long as six years. VIRAMUNE has beenshown to suppress HIV-1 in adults when used in combination withother antiretrovirals. The European Commission's approval is based on data fromseveral clinical trials. In AIDS Clinical Trial Group (ACTG) 180(BI 1100.882), a multicenter, open-label study, paediatricpatients with six weeks or less of prior nucleoside therapy weretreated with VIRAMUNE monotherapy, double therapy withVIRAMUNE/AZT (Retrovir(R), zidovudine, ZDV), or triple therapywith VIRAMUNE/AZT/ddI (Videx(R), didanosine) for 28 to 32 weeks.Patients receiving triple therapy (VIRAMUNE/AZT/ddI) maintained amedian decrease of greater than two logs below baseline in HIV-RNA for eight weeks (7 of 8 achieved a nadir of at least 1.6logs). Durable suppression of HIV-1 replication was observed oversix months of therapy in the majority of infants and childrenstudied. Complete control of HIV replication was achieved in twoinfants who began triple therapy at 2.5 months of age. In thesesubjects, HIV-1 RNA became undetectable in the plasma and theactive production of antibodies was not observed. In the majorityof patients in all three treatment groups, the percentage ofinfection-fighting CD4+ cells remained stable or increasedthrough 32 weeks of treatment. The study findings were publishedin The New England Journal of Medicine in May 1997. VIRAMUNE continues to be studied in ongoing paediatricclinical trials. Preliminary results of ACTG 356, in whichpatients took a combination of VIRAMUNE/AZT/3TC (Epivir(R),lamivudine), were presented at the Fifth Conference onRetroviruses and Opportunistic Infections in February 1998. Alsopresented were results of ACTG 245, a double-blind, randomized,placebo- controlled trial of 431 children with advanced HIVdisease. Overall, 40 percent of the children who were treatedwith a triple therapy regimen of VIRAMUNE/AZT/ddI met theprotocol-defined definition of virologic responders compared to14 percent of those just on AZT/ddI and eight percent taking onlyVIRAMUNE/ddI. Adverse event data for nevirapine-treated patients aged twomonths to 19 years indicate that VIRAMUNE is generally safe andwell tolerated. Overall, in children and adults, the mostcommonly reported adverse events associated with VIRAMUNE arerash, fever, nausea, fatigue, headache, somnolence, vomiting,diarrhoea, abdominal pain, myalgia and abnormal liver functiontests. Severe and life-threatening skin reactions andhepatotoxicity, including fatal cases of each, have occurred inpatients treated with VIRAMUNE. Granulocytopoenia is a paediatricspecific adverse event. Dosing Recommended paediatric dosing for VIRAMUNE is 4 mg/kg once-daily suspension for two weeks, followed by 7 mg/kg twice-dailyfor children between two months and eight years of age, and 4mg/kg twice-daily for children eight years and older. The totaldaily dose should not exceed 400 mg (200 mg twice-daily)suspension for any patient. VIRAMUNE can be taken with or withoutfood. VIRAMUNE tablets were approved for marketing in the EU inFebruary 1998 and have been used in more than 60,000 adultpatients world-wide. VIRAMUNE is indicated for use in combinationwith other antiretroviral agents for the treatment of HIV-1infection. This indication is based on analysis of changes insurrogate end-points, such as viral load or changes in CD4+ cellcount. VIRAMUNE should always be administered in combination withat least one additional antiretroviral agent. VIRAMUNE is a product of original research conducted atBoehringer Ingelheim Pharmaceuticals, Inc., a member of theBoehringer Ingelheim group of companies. VIRAMUNE is marketedworld-wide by Boehringer Ingelheim and in the United States byRoxane Laboratories, also a member of the Boehringer Ingelheimgroup of companies. Boehringer Ingelheim, headquartered in Ingelheim, Germany,ranks among the top 20 pharmaceutical companies in the world. Itreported revenues exceeding DM 8.75 billion in 1998. Thecorporation has some 140 affiliated entities and it conductsbusiness on every continent. Its product range is focused onhuman pharmaceuticals -- hospital, prescription and self-medication -- as well as animal health and industrialbiopharmaceuticals. The company has substantial research and development,production and distribution facilities around the globe. In 1998Boehringer Ingelheim spent over DM 1.5 billion on research anddevelopment, equivalent to 18 percent of total sales. otsOriginal Text Service: Boehringer Ingelheim Internet:http://www.newsaktuell.de Contact: Judith von Gordon ofBoehringer Ingelheim GmbH, 49-61-32-77-35-82, or fax, 49-61-32-77-66-01; or Maureen Byrne of GCI Healthcare, USA, 212-886-3312,or fax, 212-886-3291. For more information about ACTG 180, 245 orACTG 356, please call 212-886-3312

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