PR Newswire; Monday June 29, 10:30 am EST

"Typically, we have recommended that all highly active antiretroviral therapy (HAART) combinations include a protease inhibitor," said Schlomo Staszewski, M.D., director of the Outpatient Clinic for HIV-infected Patients and of the Antiretroviral Therapy Research Unit at Johann Wolfgang Goethe-University, Frankfurt am Main, Germany.

"However, the availability of a new initial HIV therapy with Sustiva that does not include a protease inhibitor, but achieves a higher level of efficacy, may provide us with a promising new alternative for patients initiating antiretroviral therapy."

Researchers presented findings from the ongoing Phase III study in which Sustiva is being evaluated in combination with two nucleoside analogues, Retrovir(R) (zidovudine, AZT) and Epivir(R) (lamivudine, 3TC), and in combination with the protease inhibitor, Crixivan(R)(indinavir). This large- scale, landmark Study 006 includes three-arms and compares the antiretroviral activity and tolerability of:

* Sustiva (600 mg, once daily) in combination with AZT (300 mg, twice daily) and 3TC (150 mg, twice daily);

* Sustiva (600 mg, once daily) in combination with Crixivan (1000 mg, every eight hours); and,

* Crixivan (800 mg, every eight hours) in combination with AZT (300 mg, twice daily) and 3TC (150 mg, twice daily).

Following are summaries of those comparisons:

Sustiva/AZT/3TC vs. Crixivan/AZT/3TC Regimen in Study 006:

--Sustiva in combination with AZT and 3TC suppressed HIV in a significantly greater proportion of patients than does Crixivan in combination with AZT and 3TC after 24 weeks of treatment, as indicated in data collected from the first 450 primarily antiretroviral-naive patients. Statistically significant superiority in the percentage of patients who achieve HIV-RNA suppression (BQL less than 400 copies/mL) for the Sustiva/AZT/3TC arm were seen at all time points between the two arms using even the most rigorous method of reporting data (an analysis referred to as "non-completer = failure"),* from as early as the second week of treatment to the end of the 24 week analysis.

--When using the traditional observed data analysis, HIV-RNA reductions to BQL were recorded in 95 percent of patients taking Sustiva/AZT/3TC. When using the most rigorous analysis for reporting data, 19.2 percent more patients receiving Sustiva/AZT/3TC achieved HIV-RNA BQL compared to patients receiving Crixivan/AZT/3TC, which was statistically significant.*

--Patients who entered the study with high viral load (>100,000 copies/mL) also experienced a greater suppression (percent BQL) with the Sustiva/AZT/3TC combination. Significantly fewer patients dropped out due to adverse events in the arms containing Sustiva, which indicates that Sustiva might also be better tolerated.

Sustiva/Crixivan Regimen in Study 006:

--Patients in the Sustiva/Crixivan arm of the study also experienced significant reductions in HIV-RNA. Eighty-six percent of patients taking this two-drug combination achieved HIV-RNA BQL, using observed data at 24 weeks.

--Patients on all three arms of Study 006 experienced CD4 cell count increases of between 115 and 134 cells/mm3 using observed data at 24 weeks. The results from the two-drug Sustiva/Crixivan arm were similar to the results from the three-drug Crixivan/AZT/3TC arm.

--Safety data from Study 006 show that Sustiva is generally well tolerated. When Sustiva is combined with either AZT/3TC or Crixivan, the most commonly reported side effects were nausea, dizziness, fatigue, impaired concentration, headache, diarrhea, rash, insomnia and dyspepsia. Severe rashes were reported in less than one percent of patients receiving Sustiva in this study.

--Long-Term Durability Data on Sustiva/Crixivan Regimen in Study 003: A second DuPont Pharmaceuticals Study 003 presented today demonstrated the significant long-term durability of the Sustiva/Crixivan regimen. Eighty-five percent of patients taking the two-drug combination maintained HIV-RNA BQL for 72 weeks, using observed data. Patients taking the Sustiva/Crixivan combination experienced a 275 cells/mm3 CD4 cell count increase using observed data at 72 weeks (240 cells/ mm3 by a more conservative method of analysis, last-observation-carried-forward)*.

"The ability to achieve significant HIV suppression in a two-drug combination including a protease inhibitor demonstrates the potency of this combination," said Sharon Riddler, M.D., assistant professor of Medicine, University of Pittsburgh (USA) School of Medicine. "These data also show that this profound HIV suppression is durable."

Overall, DuPont Pharmaceuticals states that the most commonly reported side effects include rash, nausea, dizziness, diarrhea, headache and insomnia. Severe rashes have been reported in less than one percent of patients receiving Sustiva. Pregnant women should not take this new medication unless the potential benefit to the mother outweighs the potential risk to the fetus.

Tomorrow, additional data on Sustiva will be presented at the Conference, including: Sustiva in combination with Viracept(R) (nelfinavir); more on Sustiva in combination with AZT and 3TC; and, Sustiva in a four-drug combination. Meanwhile, the company has expanded access programs for Sustiva. For information, physicians and patients may call 800-998-6854 in the U.S. and Canada, or +44-0-1462-488263 in Europe.

DuPont Pharmaceuticals submitted a New Drug Application for Sustiva to the U.S. Food and Drug Administration on June 11, 1998 and intends to submit similar marketing applications with European and Canadian regulatory authorities. DuPont Pharmaceuticals is a worldwide, research-based pharmaceutical company that markets its products under the DuPont Pharma name. DuPont announced on May 18, 1998 that it would acquire Merck's 50 percent interest in the company, which was formed in 1991.

DuPont Pharmaceuticals is focused on research, development and delivery of pharmaceuticals to treat unmet medical needs in the fight against HIV, cardiovascular disease, central nervous system disorders, cancer and arthritis-related disorders. The company is also a leader in radiopharmaceuticals.

Crixivan is a registered trademark of Merck & Co.

Retrovir and Epivir are registered trademarks of Glaxo Wellcome Inc.

Viracept is a registered trademark of Agouron.

* Last-observation-carried-forward data analysis is a method of analyzing data in which missing viral load data is assumed to be equivalent to the last recorded data for that patient. Analysis performed at only 16 and 24 weeks. Non-completer = failure data analysis is a method of reporting data in which missing data is reported as equivalent to failure (i.e., above quantifiable viral load). Only if a patient's viral load measurement is missing or unavailable at one time point in the study, the patient's results are not included in the analysis at that point -- if the patient's viral load was BQL both before and after that point.

SOURCE: DuPont Pharmaceuticals

Copyright (c) 1998/PR NewsWire. Reproduced with permission. Reproduction of this article (other than one copy for personal reference) must be cleared through the Permissions Desk, PR Newswire, 810 Seventh Avenue, New York, NY 10019.
980629
PR980613

Always watch for outdated information. This article first appeared in 1998. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 1998. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .