100 Percent of Patients Showed Suppressed HIV Replication in Cerebrospinal Fluid (CSF) with Sustiva (efavirenz) Combination Therapy, Preliminary Study Shows
-- Two Other New Studies Demonstrate Sustiva Interaction with a Protease
Inhibitor and an Antibiotic --
WILMINGTON, Del., July 2 /PRNewswire/ -- Dr. Karen Tashima and colleagues
at The Miriam Hospital, Brown University; Massachusetts General Hospital;
Harvard University; and DuPont Pharmaceuticals announced that eight HIV-
infected patients taking the investigational drug Sustiva(TM) (efavirenz) in
dual and triple combinations, achieved HIV-RNA levels in plasma and
cerebrospinal fluid (CSF) below the level of detection (less than 400
copies/mL). CSF drug levels and HIV-RNA were measured in these patients who
took Sustiva in a combination either with AZT and 3TC, or with indinavir, for
a mean duration of 26 weeks. Findings from this and several other Phase III
studies evaluating the safety and efficacy of Sustiva, an investigational,
once-daily non-nucleoside reverse transcriptase inhibitor (NNRTI), were
presented this week at the 12th World AIDS Conference in Geneva, Switzerland.
"We are encouraged that these early results show Sustiva, in combination
with other agents, suppresses HIV replication in the CSF. Since not all
antiretrovirals cross the blood-brain barrier, the ability to control viral
replication in the CSF will become increasingly critical when constructing
durable combination treatment regimens," said Karen Tashima, M.D., assistant
professor of Medicine, Brown University at The Miriam Hospital.
CSF and HIV-RNA drug levels were measured in eight patients who took
Sustiva in combination with either Retrovir(R) (zidovudine, AZT) and Epivir(R)
(lamivudine, 3TC),or Crixivan(R) (indinavir) alone, for a mean duration of
26.3 weeks. Both CSF and plasma levels of HIV-RNA were reduced to BQL at the
time samples were collected, between 19 and 38 weeks of Sustiva treatment.
Sustiva levels in the CSF achieved a mean concentration of 34.6 nM.
Pharmacokinetics of Sustiva and Norvir(R) (ritonavir):
Results from a study of Sustiva (600 mg, QD) coadministered with Norvir
(500 mg, q12h) showed that Sustiva AUC and Cmax were increased by 21 percent
and 14 percent, respectively, and ritonavir AUC and Cmax were increased by
18 percent and 24 percent, respectively. At the dose studied in uninfected
volunteers, the combination of ritonavir and efavirenz was not well tolerated
and was associated with a higher level of adverse clinical experiences and
laboratory abnormalities (elevated liver enzymes).
Pharmacokinetics of Sustiva and Rifampin:
Data presented today show rifampin reduced the efavirenz AUC, area under
the plasma concentration time curve, by 26 percent and Cmax, maximum plasma
concentration, by 20 percent in 12 uninfected volunteers. Rifampin appeared
to induce the metabolism of Sustiva in 10 of the 12 subjects; the metabolism
of Sustiva in the other two participants appeared not to be induced.
Adjustment of the dose of Sustiva is not recommended when coadministered with
rifampin, however, the clinical significance of the reduced efavirenz levels
is not known.
Virologic Resistance to Sustiva:
Results from a continued study to assess the virologic resistance profile
of Sustiva also were presented today. As indicated in earlier scientific
presentations, the study revealed that K103N was the predominant NNRTI-
resistant viral genotype observed in Sustiva-treatment failures. These data
were also presented last week at the Workshop on HIV Resistance and Treatment
Strategies in Lake Maggiore, Italy.
Other Data Presented at the 12th World AIDS Conference:
Earlier this week, data were presented at the 12th World AIDS Conference
showing:
* Sustiva given once daily in combination with AZT and 3TC in
predominantly treatment-naive patients was shown to suppress HIV in a
significantly greater proportion of patients than in patients taking
Crixivan in combination with AZT and 3TC, a standard-of-care regimen,
after 24 weeks of treatment in Study 006;
* After 72 weeks, Sustiva given once daily in combination with Crixivan
suppresses HIV to below quantifiable levels (less than 400 copies/mL)
in 85 percent of patients in Study 003;
* The combination of Sustiva with a standard-of-care three-drug regimen
(Crixivan/AZT/3TC) suppresses HIV to below quantifiable levels in a
significantly greater percentage of patients than does the three-drug
regimen alone in nucleoside analog-experienced patients in Study 020;
* Sustiva used in combination with Viracept(R) (nelfinavir) significantly
reduces HIV-RNA and elevates CD4 cell counts from baseline in both
treatment-experienced and treatment-naive patients after 16 weeks in
Study 024; and,
* All 11 treatment-naive patients randomized to Sustiva (600 mg)/AZT/3TC
who reached the 36-week time point achieved HIV-RNA BQL, in Study 005.
DuPont Pharmaceuticals reports that Sustiva is generally well tolerated in
clinical trials studying Sustiva in combination with protease inhibitors
and/or nucleoside analogue reverse transcriptase inhibitors. Commonly
reported side effects include rash, nausea, dizziness, diarrhea, headache and
insomnia. Severe rashes were 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.
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. 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 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.
Norvir is a registered trademark of Abbott Laboratories.
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.
SOURCE DuPont Pharmaceuticals
CONTACT: In Geneva, Sandra James of DuPont Pharmaceuticals,
079-206-35-07, or in U.S., 302-892-1306, or
sandra.k.james@dupontmerck.com; in U.S., Karen Carolonza of
DuPont Pharmaceuticals, 302-992-3816, or
karen.s.carolonza@dupontmerck.com; or Nikki Levy of Edelman
Worldwide, 312-240-2637, or nicole_levy@edelman.com
--------------------------------------------------------------------------------
(Today's News) (Company News On-Call) (Feature News) (Automotive)
(Entertainment) (Health/Biotech)(Technology) (Financial) (Energy)
(Washington and the World) (Money Talks) (About PRN)(Ask PRN) (Links) (PRN Events)
--------------------------------------------------------------------------------
c1998 PR Newswire. All rights reserved.
Redistribution, retransmission, republication or commercial exploitation of the contents of this site are expressly prohibited without the written consent of PR Newswire.
These pages have been optimized for Netscape v.2.0 or later |
