FDA Approves Sustiva™ (efavirenz) Capsules, First Once-daily Anti-HIV Drug

Sustiva in Combination Offers Patients a New First-line Therapy

WILMINGTON, DE (Sept. 18, 1998) DuPont Pharmaceuticals, a component of DuPont's Life Sciences Enterprise, announced today that its anti-HIV drug, Sustiva™ (efavirenz), was approved by the U.S. Food and Drug Administration (FDA). Sustiva is a once-daily non-nucleoside reverse transcriptase inhibitor (NNRTI) for treatment of HIV-1 infected individuals. The New Drug Application was submitted in June and met the FDA's fast-track criteria. Sustiva is the first anti-HIV drug to be approved by the FDA for once-daily dosing and will be used in combination with other anti-HIV drugs in both adult and pediatric patients.

"We are greatly encouraged by the clinical success of Sustiva, and welcome the introduction of this much needed once-daily anti-HIV drug," said A. Cornelius Baker, executive director, National Association of People with AIDS (NAPWA). "The clinical trial results suggest that Sustiva, when used in combination with other antiretroviral agents, may not only simplify dosing and reduce patients' pill burden, but its potency and tolerability may also offer physicians and patients, including children, new treatment options."

Results from more than a dozen clinical trials involving more than 2,000 patients demonstrate the efficacy, safety and flexibility of Sustiva. These results indicate that Sustiva reduces plasma viral RNA to below quantifiable levels (less than 400 copies/mL using the standard Amplicorª assay) in a majority of HIV-1-infected naïve and treatment-experienced individuals in two-, three-, and four-drug combinations. Studies have shown that efavirenz penetrates into the cerebrospinal fluid, a common viral sanctuary. Finally, Sustiva™ (efavirenz) can be taken only once a day with or without food; however, a high fat meal may increase the absorption of Sustiva and should be avoided.

"FDA's approval of Sustiva is excellent news for people living with HIV and AIDS," said Nicholas L. Teti, president of DuPont Pharmaceuticals. "Sustiva will be a very versatile product and provide a significant therapeutic alternative. We are also pleased the FDA review was even more rapid than our expectations."

Sustiva is priced in the mid-range of the antiretroviral class at $3,942 per year ($10.95 per day). When used in triple-combination therapy, as it was studied, Sustiva will be less expensive than the current standard of care including protease inhibitors. Sustiva will be available at pharmacies within the next few days. The company has worked with pharmacies and drug wholesalers to ensure the most rapid availability. Sustiva will be available in 200 mg capsules for adult dosing of 600 mg per day, and in 100 mg capsules and 50 mg capsules for pediatric dosing.

DuPont Pharmaceuticals conducted one of the largest and fastest enrolling antiviral Expanded Access Programs to make Sustiva available to patients who needed it while the drug was awaiting approval. To date, more than 13,000 individuals worldwide have benefited from this program. DuPont Pharmaceuticals is committed to helping patients seek reimbursement for Sustiva. The company will offer both reimbursement counseling and a comprehensive patient assistance program to ensure access to the drug for eligible patients.

The accelerated approval of Sustiva is based on analysis of plasma HIV-RNA levels and CD4 cell counts in controlled studies of up to 24 weeks in duration. At present, there are no results from controlled trials evaluating long-term suppression of HIV-RNA with Sustiva. In one study, Sustiva in combination with two nucleoside analogues (AZT and 3TC) suppressed HIV-RNA to below quantifiable levels in a greater proportion of patients than did the control arm consisting of a current standard of care regimen containing indinavir, AZT and 3TC. More subjects from the indinavir, AZT and 3TC control arm discontinued therapy because of adverse events, and this accounted for a substantial fraction of the difference between the treatment regimens. The open label design of the study makes it difficult to assess the relative efficacy of the treatment arms.

In a second study of patients with extensive prior use of nucleoside analogues, the combination of Sustiva™ (efavirenz), the protease inhibitor nelfinavir and nucleoside analogues suppressed HIV-RNA to below quantifiable levels in a higher percentage of patients than did a control arm consisting of nelfinavir and nucleoside analogues.

"We are pleased with the demonstrated success of Sustiva in a variety of rigorous clinical trials," said Paul A. Friedman, M.D., president, DuPont Pharmaceuticals Research Laboratories. "Initial HIV therapy with Sustiva in a regimen that does not include a protease inhibitor, but achieves a high level of efficacy, provides a promising new option for patients initiating antiretroviral therapy, and a viable alternative for patients unable to tolerate protease inhibitors."

Resistant virus emerges rapidly when NNRTIs are administered as monotherapy. Therefore, Sustiva must not be used as a single agent to treat HIV or added on as a sole agent to a failing regimen. Sustiva therapy should always be initiated in combination with at least one other antiretroviral agent to which the patient has not been previously exposed.

Safety data from clinical trials show Sustiva is generally well tolerated. The most significant adverse events associated with Sustiva therapy are nervous system symptoms, which are reported in approximately half of patients (e.g., dizziness, insomnia, somnolence, impaired concentration and abnormal dreaming). The discontinuation rate for nervous system symptoms was 2.6 percent. These symptoms occur early in treatment and generally resolve within a few weeks. Rarely, patients have more serious side effects that may affect mood or ability to think clearly. Mild to moderate skin rash was reported in approximately one out of four patients. The incidence of severe rash was less than 1 percent. The discontinuation rate for rash in clinical trials was 1.7 percent.

Women should not become pregnant while taking Sustiva™ (efavirenz) because birth defects have been seen in animals given Sustiva.

For questions about Sustiva, physicians and patients may call 1-800-4PHARMA (1-800-474-2762), or visit the company's website at www.sustiva.com. DuPont Pharmaceuticals is currently seeking regulatory approval in Europe, having submitted an application for marketing clearance in June. Submission for approval has also been made to Canadian regulatory authorities.

DuPont Pharmaceuticals, a wholly owned subsidiary of DuPont, is a worldwide, research-based pharmaceutical company that markets its products under the DuPont Pharma name. The business focuses 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. DuPont Pharmaceuticals is also a leader in medical imaging.

Founded in 1802, DuPont is a global research and technology-based life sciences, materials and energy company. Committed to better things for better living, DuPont serves worldwide markets including food and nutrition; health care; agriculture; fashion and apparel; home and construction; electronics; transportation and energy. The company operates in about 70 countries and has 98,000 employees. Revenues in 1997 were more than $45 billion.



Amplicor is a trademark of Roche Laboratories