Philadelphia, Pa. - Oct. 31, 2000 - Aslera™, an investigational drug, significantly improves disease activity and symptoms of patients with the chronic autoimmune disease systemic lupus erythematosus (SLE or lupus), according to a Phase III placebo-controlled, double-blind multicenter study presented at the 64th Annual Scientific Meeting of the American College of Rheumatology in Philadelphia. Aslera™ (GL701 or prasterone) is developed by Genelabs Technologies, Inc. (Nasdaq:GNLB).
"This study is particularly significant because it shows that GL701 is a promising new drug for people with lupus. The trial demonstrated clinically important benefits including improved disease activity and symptoms and improved bone mineral density for women on steroids. Current lupus treatment primarily relies on the chronic use of steroids, such as prednisone, that can have many serious adverse consequences for a lupus patient's health and quality of life," says Robert G. Lahita, M.D., coauthor of the study, Professor of Medicine, Saint Vincent's Medical Center, New York Medical College. "Furthermore, because lupus has been a very difficult disease to study, the GL701 clinical trial represents a breakthrough in the design of studies for new treatments for SLE."
In the study, Lahita and his colleagues compared Aslera™ to placebo among 381 women who had mild to moderate lupus. Patients were evaluated in a randomized double-blind comparison of Aslera™, 200 mg or placebo daily for 12 months. Study criteria required that patients have active disease at baseline and permitted patients to remain on background therapy such as the corticosteroid prednisone, however prednisone dosage at study entry was limited to no more than 10 mg/day. In the study, the primary endpoint was proportion of responders, which was defined as improvement or stabilization, compared to baseline (allowing for small instrument variability), for all four scoring instruments: Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and Systemic Lupus Activity Measure (SLAM), which measure disease activity; and the Krupp Fatigue Severity Score (KFSS) and Patient Visual Analog Scale (VAS), which measure quality of life parameters. In addition, for a patient to be a responder she could not have experienced clinical deterioration. The treatment groups were well balanced for baseline characteristics.
The Aslera™ group had significantly more responders, 66 percent vs. 49 percent on placebo (p=0.005). Also, there was a consistent trend in favor of Aslera™ among other efficacy variables including flare and the individual scoring instruments.
In this study, Aslera™ was well tolerated. Adverse events were generally mild. Aslera™ patients experienced higher rates than those on placebo of acne (33 percent vs. 14 percent) and hirsutism (16 percent vs 2 percent), but most cases of each condition were mild. In contrast, patients on placebo therapy had more muscle pain, 36 percent vs. 22 percent on Aslera™, and mucosal ulcers, 23 percent vs.15 percent on Aslera™, both of which are symptoms of lupus. Lipid levels, including total cholesterol, HDL cholesterol and triglycerides, decreased in the group of patients receiving Aslera™, compared to the placebo group. A decrease in triglycerides may be beneficial because high levels of triglycerides are associated with increased cardiovascular risk. There were five deaths among study participants, all in the placebo group, including two suicides. Four of the deaths were possibly related to the patients' lupus, investigators note.
Separately, bone mineral density (BMD) was assessed among 37 patients who were on long-term prednisone treatment. Patients in the Aslera™ group demonstrated significant improvement in their BMD levels. Specifically, 18 Aslera™ patients showed increases in spinal BMD of 1.8 percent in comparison to 19 placebo patients who showed a loss of 1.8 percent (p=0.004). Hip scores demonstrated differences as well, with an increase of 2.1 percent in Aslera™ patients compared to a loss of 0.2 percent among placebo patients (p=0.080).
"The significant improvement in symptoms that lupus patients experience while taking Aslera � reinforces its potential as a new lupus therapy. If approved by the Food and Drug Administration (FDA), GL701, which will be marketed under the name Aslera™, will provide lupus patients with the first new treatment for their chronic, debilitating disease in 40 years," said Marc Gurwith, M.D., Genelabs Vice President, Drug Development and Chief Medical Officer. The company completed its submission to the FDA of its New Drug Application (NDA) for marketing approval of Aslera™ in September 2000. The Aslera™ NDA was granted priority review designation by FDA in October 2000, which generally provides for a six-month review period.
In lupus, the body develops antibodies that react against a person's normal tissue, which can lead to inflammation, arthritis pain, tissue injury and major organ damage. Common signs and symptoms of disease that lupus sufferers experience - severe fatigue, arthritis, facial rash, fever, seizures, headache, muscle weakness, memory loss, hair loss, and photosensitivity - can lead to a poor quality of life. Lupus can be mild but also can cause significant and potentially serious damage to organs such as the lungs, heart, kidney, and brain. The disease is characterized by flares of disease activity interspersed with periods of improvement or remission.
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. Lupus primarily affects women, many of whom experience the initial onset in their late teens and early twenties.
Lahita's coauthors include Philip J. Mease, M.D., of Minor & James Medical, PLLC, Seattle, WA; Joan T. Merrill, M.D., assistant professor, St. Luke's-Roosevelt Medical Center, New York, NY; Michelle A. Petri, M.D., M.P.H., associate professor of rheumatology at The Johns Hopkins School of Medicine, Baltimore, MD; Ellen M. Ginzler, M.D., professor and chief of rheumatology at the State University of New York Medical Center, Brooklyn, NY; Robert S. Katz, M.D., Rheumatology Associates, Chicago, IL; Oscar S. Gluck, M.D., Arizona Rheumatology Center, Phoenix, AZ; and Kenneth E. Schwartz, M.D., Senior Medical Director, and Marc Gurwith, M.D., Vice President, Drug Development and Chief Medical Officer, both at Genelabs, Redwood City, CA.
Genelabs Technologies, Inc. is a biopharmaceutical company engaged in the discovery and development of a new class of pharmaceutical products that selectively regulate gene expression or inactivate pathogens by binding directly to DNA or RNA, the fundamental material of genes. By acting directly on the genetic material, Genelabs' technology can be applicable to a wide range of therapeutic applications including diseases such as cancer and autoimmune disorders and infectious diseases caused by bacteria and viruses. Originally licensed from Stanford University, the company has completed the clinical development of Aslera™, which is under review by the FDA for US marketing approval. Genelabs is seeking approval of Aslera™ as new treatment for women with mild to moderate SLE.
NOTE: Except for historical information, the statements in this news release are forward-looking and are subject to uncertainties and risks that could cause actual results to differ materially from the statements made. Uncertainties and risks include, without limitation, whether the results of the company's clinical trials of Aslera™ and other supporting information will be sufficient to support the approval of Aslera™ by FDA; delays regarding the regulatory approval process including the timing and scope of approval received, if any; uncertainties and risks regarding market acceptance of Aslera™ as a treatment for SLE; the company's limited manufacturing and marketing experience; the validity, scope and enforceability of patents related to Aslera™; the company's capital requirements and history of operating losses; and uncertainties and risks regarding the company's ability to raise needed additional capital or consummate strategic or corporate partner transactions on favorable terms or at all. The active ingredient in Aslera™ is prasterone, the synthetic equivalent of the androgenic hormone dehydroepiandrosterone (DHEA). Products containing DHEA are currently being marketed by others as dietary supplements. The company has not submitted applications for regulatory review outside the US. In addition, neither U.S. nor foreign regulatory authorities have made a determination as to the safety or efficacy of Aslera™ for SLE. Please see the information appearing in the company's filings with the Securities and Exchange Commission for more discussion regarding these uncertainties and risks and those associated with the company's research programs, early stage of development and other risks which may affect the company. The company does not undertake any obligation to update these forward-looking statements to reflect events or circumstances after the date of this release.
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