Results of Landmark Studies Support Use of AIDS Drug VIRAMUNE(R) (nevirapine)

Ingelheim, Germany (PROTEXT) - Data Presented on ProteaseInhibitor-Sparing Trials and HIVNET 012 Study for the Preventionof Mother-to-Child HIV Transmission. A distinguished panel of HIV researchers presented results ofthree important VIRAMUNE (nevirapine) trials today during asymposium at the 7th European Conference on Clinical Aspects andTreatment of HIV-Infection in Lisbon. New findings support theuse of regimens, which include the potent anti-HIV drug, VIRAMUNE(nevirapine), for three very distinct patient populations. VIRAMUNE is a non-nucleoside reverse transcriptase inhibitor(NNRTI), commonly used in combination therapy to treat adult andpediatric HIV-infection. VIRAMUNE requires two pills per day andcan be taken with no food restrictions once- or twice-daily(once-daily dosing not yet approved; currently under clinicalinvestigation). "The data presented here today provide insight into potent andpractical methods for combating HIV infection for variouspatient populations," said the symposium chair, Professor JoepLange, National AIDS Therapy Evaluation Centre, Amsterdam."Topics addressed major issues, such as choosing first-linetreatment regimens, preventing mother-to-child HIV transmissionin the developing world and reversing the effects oflipodystrophy, a common side effect of protease inhibitors." Atlantic Study Supports "Protease-Sparing" Strategy Professor Lange discussed updated findings of the multi-center, international Atlantic Study, the first head-to-headcomparison trial of agents in the three currently availableclasses of HIV/AIDS drugs. The 48-week analysis shows that VIRAMUNE given once-a-day incombination with two other antiretroviral drugs (ddI* and d4T*)is as potent as a triple combination regimen of a proteaseinhibitor given three times daily with ddI and d4T. "These long-term results demonstrate that treatmentcombinations containing VIRAMUNE are as effective as proteaseinhibitor-containing regimens in reducing HIV viral loads toundetectable levels in patients -- even in those who had highlevels of HIV when they initiated treatment," said lead Atlanticinvestigator, Professor Joep Lange. The treatment combinations evaluated in the Atlantic studyconsist of the nucleoside analogues ddI and d4T combined witheither once-daily VIRAMUNE (an NNRTI), thrice-daily indinavir*(a protease inhibitor) or twice-daily 3TC* (a nucleosideanalogue). A total of 235 patients who have completed 48 weeksof the study; HIV RNA measures are available for 181 of thesepatients. In the "as-treated analysis," which accounts for patients whodid not stop therapy due to toxicity or loss to follow-up, thepercentage of patients with HIV-1 RNA <500 copies/ml was 91% inthe VIRAMUNE arm, 95% in the indinavir arm and 90% in the 3TCarm. The percentage with undetectable HIV-1 RNA <50 copies/mlwas 82% in the VIRAMUNE arm, 90% in the indinavir arm and 78% inthe 3TC arm. Using an "intent-to-treat analysis" accounting forall patients, including those who stopped treatment before theend of the study, the percentage of patients with undetectableHIV-1 RNA (<50 copies/ml) at 48 weeks was 51% in the VIRAMUNEarm, 57% in the indinavir (protease inhibitor) arm and 49% in the3TC (nucleoside analogue) arm. Professor Lange also discussed results of an additionalanalysis of the Atlantic study, which evaluated patients withhigher baseline levels of the virus in their blood (>51,286copies/ml). In these participants, the VIRAMUNE regimen was alsoas effective at reducing levels of HIV as the protease inhibitorregimen, with 50% and 55% of patients reaching undetectablelevels of HIV, respectively. In the 3TC arm, only 32% ofpatients with higher baseline viral loads reached undetectablelevels of HIV. Safety data indicated that all treatment arms were safe andgenerally well tolerated with similar adverse events in allarms. Researchers plan to follow patients for more than 144weeks. VIRAMUNE for preventing Mother-to-Child HIV transmission indeveloping nations Encouraging preliminary results of a trial conducted in Ugandaby the National Institute of Allergy and Infectious Disease's(NIAID) HIV Prevention Trials Network (HIVNET) were presented byDr. Phillipa Musoke. Findings demonstrate that VIRAMUNE safelyand effectively reduced HIV transmission from mothers to theirinfants. A simple, inexpensive regimen of one oral dose ofVIRAMUNE given to an HIV-infected woman in labor and another toher newborn within three days of birth was almost twice aseffective in reducing mother-to-infant HIV transmission as ashort course of the drug ZDV*. The study, known as HIVNET 012, compared the safety andefficacy of two different short course regimens ofantiretroviral drugs administered late in pregnancy. The VIRAMUNEregimen consisted of a single 200 mg tablet given to mothers inlabor and a single 2 mg/kg dose of VIRAMUNE oral suspension tothe newborns within 72 hours after delivery. The ZDV regimen was600 mg at the onset of labor, 300 mg every three hours duringlabor, and 4 mg/kg of ZDV twice-daily to the newborn for thefirst seven days after delivery. All women entered into thestudy were in their ninth month of pregnancy and had notpreviously taken any antiretroviral drugs. For the interim analysis, the study team looked at data from618 mothers (308 receiving ZDV and 310 receiving VIRAMUNE) andtheir infants. The incidence of HIV infection in the VIRAMUNEbabies was about half of that of the ZDV patients -- at 14 to 16weeks of age, 13.1 percent of infants who received VIRAMUNE werefound to be infected with HIV, compared with 25.1 percent ofthose in the ZDV group. Both drugs appeared to be safe and well-tolerated. The mothers and their infants will continue to beactively followed until the babies are 18 months old. NIAID researchers chose VIRAMUNE for the study because of itspotency, pharmacokinetic profile and affordability.Additionally, it can be stored at room temperature, an importantconsideration in developing countries. Data regarding the safetyand efficacy of VIRAMUNE for prevention of perinatal HIVtransmission has not been reviewed by regulatory agencies. Switching to a VIRAMUNE-based combination may decreaseLipodystrophy Increases in cholesterol and triglyceride levels andlipodystrophy (abnormal distribution of body fat) is becoming acommon side effect seen in patients being treated with proteaseinhibitors. Results of a multicenter, prospective, randomised studyconducted by Dr. Lidia Ruiz and her colleagues from Barcelona,Spain showed that switching patients from a protease inhibitor-containing regimen to a VIRAMUNE-containing regimen significantlydecreased their cholesterol and triglyceride levels. Thepatients who switched to VIRAMUNE also reported an improvedquality of life and appearance in body shape. All patients enrolled in the study had been taking the samecombination of antiretroviral agents (d4T+3TC+a proteaseinhibitor) for at least nine months, had maintained HIV-RNA viralload <400 copies/ml and >100 CD4+ cells for at least 6 monthsand were suffering clinically evident lipodystrophy. Patientswere randomised to either group 1 (d4T+3TC+VIRAMUNE) or group 2(d4T+3TC+protease inhibitor). Sixty-three (31 in group 1; 32 in group 2) out of 106 studyparticipants have completed 24 weeks of the study. Most patients(51/56) had baseline plasma viral load <50 copies/ml andmaintained this level of suppression through week 24. CD4+ cellcounts increased significantly in similar amounts in both groupsby week 24. In the VIRAMUNE group, cholesterol and triglyceridelevels diminished significantly with respect to the baselinevalues. Cholesterol levels went from 224+/-49 to 203+/-37; triglyceride levels went from267+/-183 to 210+/-154. These changes were not observed in theprotease inhibitor group. VIRAMUNE Background VIRAMUNE was the first member of the NNRTI class of anti-HIV/AIDS drugs to be approved. VIRAMUNE is indicated as part ofa combination therapy for the antiviral treatment of HIV-1infected adult patients with advanced or progressiveimmunodeficiency. Combining three or more antiretroviral agentsis the standard of care for people infected with HIV. Thisindication is based on analysis of changes in surrogate end-points. VIRAMUNE is generally well-tolerated. The most commonlyreported adverse events associated with VIRAMUNE are rash,fever, nausea, headache and abnormal liver function tests.Severe and life-threatening skin reactions and hepatotoxicity,including fatal cases of each, have occurred in patients treatedwith VIRAMUNE. 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 Corporation, with headquarters inIngelheim (Germany) is one of the 20 leading pharmaceuticalcorporations in the world. It reported revenues exceeding DEM 8.7billion in 1998. The corporation has more than 140 affiliated companies and itconducts business on every continent. Its product range isfocused on human pharmaceuticals -- hospital, prescription andself-medication -- as well as animal health. The group of companies has substantial research anddevelopment, production, and distribution facilities around theglobe. In 1998 the Boehringer Ingelheim Corporation spent DEM1.6 billion on R&D, equivalent to 18% of total sales. For more information on Boehringer Ingelheim please see alsoits Internet web page http://www.boehringer-ingelheim.com. * antiretroviral drugs mentioned in this release: d4T (Zerit(R), stavudine) and ddI (Videx(R), didanosine),Bristol Myers Squibb indinavir (Crixivan(R)), Merck & Co. 3TC (Epivir(R), lamivudine) and ZDV (zidovudine, AZT,Retrovir(R)), Glaxo Wellcome Inc. ots Original Text Service:Boehringer Ingelheim GmbH Internet: http://www.newsaktuell.deContact: Judith von Gordon, Corporate Public Relations Divisionof Boehringer Ingelheim GmbH, +49-6132-773582, fax, +49-6132-776601; or Maureen Byrne, (USA) 212-886-3312, or DeniseConnolly, (USA) 212-886-3117, both of GCI Healthcare, fax, (USA)212-886-3291, for Boehringer Ingelheim GmbH Web site:http://www.boehringer-ingelheim.com

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