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

Ingelheim, Germany (ots-PRNewswire) - Data Presented on Protease Inhibitor-Sparing Trials and HIVNET 012 Study for the Prevention of Mother-to-Child HIV Transmission.

A distinguished panel of HIV researchers presented results of three important VIRAMUNE (nevirapine) trials today during a symposium at the 7th European Conference on Clinical Aspects and Treatment of HIV-Infection in Lisbon. New findings support the use 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 and pediatric HIV-infection. VIRAMUNE requires two pills per day and can be taken with no food restrictions once- or twice-daily (once-daily dosing not yet approved; currently under clinical investigation).

"The data presented here today provide insight into potent and practical methods for combating HIV infection for various patient populations," said the symposium chair, Professor Joep Lange, National AIDS Therapy Evaluation Centre, Amsterdam. "Topics addressed major issues, such as choosing first-line treatment regimens, preventing mother-to-child HIV transmission in the developing world and reversing the effects of lipodystrophy, 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-head comparison trial of agents in the three currently available classes of HIV/AIDS drugs.

The 48-week analysis shows that VIRAMUNE given once-a-day in combination with two other antiretroviral drugs (ddI* and d4T*) is as potent as a triple combination regimen of a protease inhibitor given three times daily with ddI and d4T.

"These long-term results demonstrate that treatment combinations containing VIRAMUNE are as effective as protease inhibitor-containing regimens in reducing HIV viral loads to undetectable levels in patients -- even in those who had high levels of HIV when they initiated treatment," said lead Atlantic investigator, Professor Joep Lange.

The treatment combinations evaluated in the Atlantic study consist of the nucleoside analogues ddI and d4T combined with either once-daily VIRAMUNE (an NNRTI), thrice-daily indinavir* (a protease inhibitor) or twice-daily 3TC* (a nucleoside analogue). A total of 235 patients who have completed 48 weeks of the study; HIV RNA measures are available for 181 of these patients.

In the "as-treated analysis," which accounts for patients who did not stop therapy due to toxicity or loss to follow-up, the percentage of patients with HIV-1 RNA <500 copies/ml was 91% in the VIRAMUNE arm, 95% in the indinavir arm and 90% in the 3TC arm. The percentage with undetectable HIV-1 RNA <50 copies/ml was 82% in the VIRAMUNE arm, 90% in the indinavir arm and 78% in the 3TC arm. Using an "intent-to-treat analysis" accounting for all patients, including those who stopped treatment before the end of the study, the percentage of patients with undetectable HIV-1 RNA (<50 copies/ml) at 48 weeks was 51% in the VIRAMUNE arm, 57% in the indinavir (protease inhibitor) arm and 49% in the 3TC (nucleoside analogue) arm.

Professor Lange also discussed results of an additional analysis of the Atlantic study, which evaluated patients with higher baseline levels of the virus in their blood (>51,286 copies/ml). In these participants, the VIRAMUNE regimen was also as effective at reducing levels of HIV as the protease inhibitor regimen, with 50% and 55% of patients reaching undetectable levels of HIV, respectively. In the 3TC arm, only 32% of patients with higher baseline viral loads reached undetectable levels of HIV.

Safety data indicated that all treatment arms were safe and generally well tolerated with similar adverse events in all arms. Researchers plan to follow patients for more than 144 weeks.

VIRAMUNE for preventing Mother-to-Child HIV transmission in developing nations

Encouraging preliminary results of a trial conducted in Uganda by the National Institute of Allergy and Infectious Disease's (NIAID) HIV Prevention Trials Network (HIVNET) were presented by Dr. Phillipa Musoke. Findings demonstrate that VIRAMUNE safely and effectively reduced HIV transmission from mothers to their infants. A simple, inexpensive regimen of one oral dose of VIRAMUNE given to an HIV-infected woman in labor and another to her newborn within three days of birth was almost twice as effective in reducing mother-to-infant HIV transmission as a short course of the drug ZDV*.

The study, known as HIVNET 012, compared the safety and efficacy of two different short course regimens of antiretroviral drugs administered late in pregnancy. The VIRAMUNE regimen consisted of a single 200 mg tablet given to mothers in labor and a single 2 mg/kg dose of VIRAMUNE oral suspension to the newborns within 72 hours after delivery. The ZDV regimen was 600 mg at the onset of labor, 300 mg every three hours during labor, and 4 mg/kg of ZDV twice-daily to the newborn for the first seven days after delivery. All women entered into the study were in their ninth month of pregnancy and had not previously taken any antiretroviral drugs.

For the interim analysis, the study team looked at data from 618 mothers (308 receiving ZDV and 310 receiving VIRAMUNE) and their infants. The incidence of HIV infection in the VIRAMUNE babies was about half of that of the ZDV patients -- at 14 to 16 weeks of age, 13.1 percent of infants who received VIRAMUNE were found to be infected with HIV, compared with 25.1 percent of those in the ZDV group. Both drugs appeared to be safe and well-tolerated. The mothers and their infants will continue to be actively followed until the babies are 18 months old.

NIAID researchers chose VIRAMUNE for the study because of its potency, pharmacokinetic profile and affordability. Additionally, it can be stored at room temperature, an important consideration in developing countries. Data regarding the safety and efficacy of VIRAMUNE for prevention of perinatal HIV transmission has not been reviewed by regulatory agencies.

Switching to a VIRAMUNE-based combination may decrease Lipodystrophy

Increases in cholesterol and triglyceride levels and lipodystrophy (abnormal distribution of body fat) is becoming a common side effect seen in patients being treated with protease inhibitors.

Results of a multicenter, prospective, randomised study conducted 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 significantly decreased their cholesterol and triglyceride levels. The patients who switched to VIRAMUNE also reported an improved quality of life and appearance in body shape.

All patients enrolled in the study had been taking the same combination of antiretroviral agents (d4T+3TC+a protease inhibitor) for at least nine months, had maintained HIV-RNA viral load <400 copies/ml and >100 CD4+ cells for at least 6 months and were suffering clinically evident lipodystrophy. Patients were 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 study participants have completed 24 weeks of the study. Most patients (51/56) had baseline plasma viral load <50 copies/ml and maintained this level of suppression through week 24. CD4+ cell counts increased significantly in similar amounts in both groups by week 24. In the VIRAMUNE group, cholesterol and triglyceride levels diminished significantly with respect to the baseline values. Cholesterol levels

went from 224+/-49 to 203+/-37; triglyceride levels went from 267+/-183 to 210+/-154. These changes were not observed in the protease 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 of a combination therapy for the antiviral treatment of HIV-1 infected adult patients with advanced or progressive immunodeficiency. Combining three or more antiretroviral agents is the standard of care for people infected with HIV. This indication is based on analysis of changes in surrogate end-points.

VIRAMUNE is generally well-tolerated. The most commonly reported 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 treated with VIRAMUNE.

VIRAMUNE is a product of original research conducted at Boehringer Ingelheim Pharmaceuticals, Inc., a member of the Boehringer Ingelheim group of companies. VIRAMUNE is marketed world-wide by Boehringer Ingelheim and in the United States by Roxane Laboratories, also a member of the Boehringer Ingelheim group of companies.

Boehringer Ingelheim Corporation, with headquarters in Ingelheim (Germany) is one of the 20 leading pharmaceutical corporations in the world. It reported revenues exceeding DEM 8.7 billion in 1998.

The corporation has more than 140 affiliated companies and it conducts business on every continent. Its product range is focused on human pharmaceuticals -- hospital, prescription and self-medication -- as well as animal health.

The group of companies has substantial research and development, production, and distribution facilities around the globe. In 1998 the Boehringer Ingelheim Corporation spent DEM 1.6 billion on R&D, equivalent to 18% of total sales.

For more information on Boehringer Ingelheim please see also its 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.de

Contact:
Judith von Gordon,
Corporate Public Relations Division of Boehringer
Ingelheim GmbH, +49-6132-773582, fax, +49-6132-776601; or
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Denise Connolly, (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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