Genelabs Technologies Inc reported that its investigational drug GL701 (prasterone, dehydroepiandrosterone) can stabilize or improve disease symptoms for patients with systemic lupus erythematosus (SLE or lupus), based on statistically significant results from its second Phase III clinical trial.

The data are being presented at the Clinical Trial Symposium at ENDO 2000, the 82nd Annual Meeting of The Endocrine Society in Toronto, Canada.

Kenneth E. Schwartz, a board certified endocrinologist and Genelabs Senior Medical Director said, ``This study is particularly significant because it shows that GL701 is potentially a promising new hormonal therapy as a first line treatment for people with lupus. Current treatment is primarily with chronic use of steroids, such as prednisone, which have many serious adverse consequences.''

SLE is a serious autoimmune disease that primarily affects women, many of whom experience the initial onset of disease in their late teens and early twenties. It is characterized by systemic autoimmunity leading to inflammation that can affect a number of organ systems and by alterations in androgen/estrogen metabolism. Approximately 200,000 people in the United States and more than one million worldwide have lupus, according to U.S. government and private sector statistics.

The reported trial is the largest double blind, randomized, placebo-controlled clinical study of the safety and effectiveness for a lupus treatment ever completed. The study evaluated patients' disease activity; organ damage; quality of life, such as severity of fatigue and the ability to conduct daily activities; and bouts of heightened disease symptoms, called flares.

The objective of this pivotal Phase III study was to determine whether GL701 would improve SLE disease activity and/or its symptoms in women with clinically active disease, which was principally measured by response to treatment. Response to treatment, the study's primary endpoint, was defined as improvement or stabilization of SLE disease activity and symptoms in each of four scoring instruments, with allowance for minor variability and with no clinical deterioration. Patients in the group treated with GL701 had a statistically significant greater rate of response than the group that received placebo.

Patients treated with GL701 showed a 35 percent greater response rate than the placebo group (p=0.005): 66 percent of patients (87/132) responded to treatment with GL701 compared to 49 percent (65/133) for patients who received placebo. The study showed a trend toward a reduction in the incidence of disease flare, a serious manifestation of lupus, which was more than 24 percent lower in the GL701 patient group (31/132) compared to patients who received placebo (41/133).

Further evidence from the trial demonstrated that GL701 significantly increased bone density, compared to placebo, in patients receiving chronic corticosteroid therapy. Bone density measurements, using the Dual X-ray Absorptiometry (DXA) test, were taken at 8 of the trial's 27 investigator sites. Thirty-seven SLE patients were evaluated for mean changes in bone density of both the lumbar spine and hip. These patients had been on steroids for at least six months prior to entry in the study. In this study, 18 lupus patients on chronic steroid therapy who received GL701 demonstrated a statistically significant increase in mean bone density in lumbar spine, compared to 19 patients receiving placebo (p=0.004). Mean bone density in the spine increased 1.83 percent in patients on GL701 vs. a decrease of 1.78 percent in placebo patients. GL701 also demonstrated improved changes in mean bone density of the hip. Total hip mean bone density increased 2.08 percent in patients receiving GL701 and decreased 0.16 percent in placebo patients (p=0.080).

GL701 appears to be well tolerated. In this trial adverse events were reported in both the placebo and the treatment group. Adverse events associated with GL701 were generally mild and expected and included acne, facial hair growth and hormonal changes. Some ailments commonly associated with lupus and reported as adverse events were less frequent in patients who were treated with GL701 compared with patients who received placebo. In patients receiving GL701, there was a statistically significant decrease in high-density lipoprotein (HDL) cholesterol. On the other hand, there was also a statistically significant reduction in triglycerides, a lipid that in high levels may increase risk of heart disease. Underscoring the serious nature of lupus, there were 5 deaths, including 2 suicides, among patients in the study. All of the deaths were in the placebo group. The findings from this Phase III trial confirmed the tolerability of GL701 seen in other studies in patients with lupus.

NDA Clinical Sections Submitted

Genelabs is seeking approval of GL701 as a first line therapy for women with active SLE to stabilize or improve their disease signs and symptoms, and also for SLE patients who are corticosteroid dependent, to reduce their corticosteroid dose -- the primary endpoint of the first Phase III clinical trial of GL701 conducted by Genelabs.

James A.D. Smith, Genelabs President and Chief Executive Officer said, ``Based on the encouraging results of our two pivotal trials of GL701 for SLE, we recently submitted the clinical sections of the New Drug Application (NDA) for marketing approval in the United States and we are on schedule to submit the remaining sections in the second half of this year. The FDA has granted fast track designation for GL701 and has agreed that our NDA would be submitted on a rolling basis. If approved, GL701 will be the first new treatment for lupus patients in 40 years.''