Prestara™, (known in development as GL701) Genelabs' investigational drug for systemic lupus erythematosus (SLE or lupus), is a pharmaceutical preparation that contains prasterone, a synthetic form of the human hormone dehydroepiandrosterone (DHEA) as its active ingredient.

Clinical Rationale Behind Prestara™

Dehydroepiandrosterone (DHEA) is a naturally occurring hormone produced by the adrenal glands. It is secreted primarily as its metabolite, DHEA-sulfate (DHEA-S), which is the most abundant circulating adrenal steroid in human blood.

Lupus patients with active disease generally have low blood levels of DHEA. Early studies at Stanford University indicated that oral use of DHEA may be beneficial in the treatment of SLE. A Phase II clinical study, conducted at Stanford and published in Arthritis and Rheumatism, indicated that patients treated with DHEA showed improvement demonstrated by the patients' own assessments, their physicians' clinical assessments, and a commonly accepted disease activity index, while patients treated with placebo did not show improvement. In addition, the mean prednisone (a commonly used glucocorticoid) dose was decreased in patients treated with DHEA. Genelabs licensed patent rights from Stanford as a result of these findings.

Genelabs' Clinical Program for Prestara™

Genelabs filed an Investigational New Drug application (IND) with the Food and Drug Administration (FDA) in December 1993. In May 1994, the company started its first Phase II/III clinical trial (Study GL94-01), a randomized, double-blind, placebo-controlled, multi-center study for the treatment of mild to moderate SLE in women who require treatment with prednisone or other steroids. The study was designed to determine whether Prestara would allow steroid-dependent SLE patients to reduce their prednisone dose to 7.5 mg per day or less (a near-physiologic level) while either improving or stabilizing their disease activity. In March 1996, the company initiated a second Phase III clinical trial (Study GL95-02) of Prestara in women with mild to moderate lupus. The objective of the study was to determine whether Prestara would improve or stabilize SLE disease activity and/or its symptoms in women with clinically active lupus. Nested within Study GL95-02 was a study to measure the effect of Prestara on bone mineral density. Upon completion of Study GL95-02, Genelabs prepared a new drug application (NDA) for Prestara to treat women with lupus, which was submitted to the FDA in 2000.

In August 2002 the agency issued an approvable letter for the Prestara NDA. The letter stated that approval of Prestara was primarily contingent upon the successful completion of an additional clinical trial providing sufficient evidence to confirm the positive effect of Prestara on bone mineral density in women with lupus taking glucocorticoids that was observed in Study GL95-02. In August 2004 Genelabs completed an additional Phase III trial, Study GL02-01, which was designed to confirm the positive bone mineral density results observed in Study GL95-02. Results from this 6-month trial indicated that Prestara did not demonstrate a statistically significant difference between the bone mineral density in the group of patients taking Prestara and the group taking placebo, although a beneficial trend was observed in the study. An open-label follow-on clinical trial (Study GL03-01), in which patients received one of two different doses of Prestara, met its primary endpoint of maintaining the bone mineral density of the women receiving the therapeutic dose (200 mg/day) of Prestara in the trial.

After discussing all of these results with the FDA, Genelabs announced in January 2006 that the FDA had indicated that one additional, adequate, well-controlled phase III clinical trial would be necessary to support an indication for the treatment of the signs and symptoms of lupus. Separately, the FDA indicated that additional positive prospective phase III clinical trial data would be necessary before the FDA would consider reviewing an NDA for BMD in lupus. Based on this information, Genelabs plans to pursue an indication for treating the signs and symptoms of lupus, rather than BMD, and is in the process of designing a clinical trial protocol for an additional study, although the company does not believe that it will conduct the study on its own.

Back to top

© Genelabs Technologies, Inc. All rights reserved. - Terms of Use