Genelabs Technologies Inc. has laid the groundwork for a confirmatory Phase III trial of its lupus drug, Prestara, and said it expects to begin the trial before the end of the year.
"The endpoint will be bone mineral density measured at the lumbar spine, which is what we looked at in previous Phase III studies," said Matthew Loar, chief financial officer. "This is what the FDA has said should be interpreted for this confirmatory trial."
With the trial protocol, Genelabs, of Redwood City, Calif., has scaled another wall in its path through the FDA's obstacle course. After its initial new drug application filing in 2000, the drug went before a review panel that did not vote on whether to approve the drug or not, and the company received a not-approvable letter from the FDA in 2001. Genelabs said at the time the not-approvable letter was due to interpretations of data. In late August, the FDA completed its review of the Prestara NDA and the company received an approvable letter for Prestara, with the stipulation that confirmatory Phase III trial be conducted. (See BioWorld Today, June 28, 2001, and Sept. 3, 2002.)
Genelabs' stock (NASDAQ:GNLB) rose 25 cents Friday, or 17.9 percent, to close at $1.65.
The proposed trial is a multicenter, randomized, placebo-controlled, double-blind study. About 110 women with systemic lupus erythematosus receiving glucocorticoids are expected to be enrolled in the U.S. and treated for six months.
The trial is the most significant of the FDA's requests, but as the trial progresses, Genelabs will be "addressing the other issues in the approvable letter," Loar told BioWorld Today, including aspects of manufacturing.
The timing of a full response to the FDA's letter will depend on the duration of enrolling patients, but Loar said Genelabs would "work with a number of centers to [conduct the trial] as expeditiously as possible."
Prestara (prasterone), formerly called GL701 and also Aslera, contains prasterone, a synthetic form of the human hormone dehydroepiandrosterone (DHEA), as its active ingredient. Lupus patients with active disease generally have low blood levels of DHEA. North American rights for the product have been licensed to Watson Pharmaceuticals Inc., of Corona, Calif., and Genelabs is in discussions with companies for European and Japanese rights. It plans to have its marketing application filed in Europe by the end of the year.
The company has completed two Phase III trials. In the study called GL95-02, baseline and post-treatment measurements of bone mineral density were taken in women with lupus on low-dose glucocorticoids. The mean percentage change in bone mineral density of both the lumbar spine and hip significantly increased in the group of patients treated with Prestara, compared to decreases in the placebo group. The differences between groups were statistically significant, favoring Prestara at both the lumbar spine (p=0.003) and hip (p=0.013). That trial had a 12-month duration.
Lupus is an autoimmune disease that can affect the musculoskeletal and nervous systems, as well as the lungs, heart, kidneys, skin and joints. There has not been a new drug approved to treat the affliction in more than 40 years. Genelabs hopes to change that.
"[Beginning the trial] is an important milestone, since it is one more step to getting the product approved, if the results are positive," Loar said.
Genelabs' other efforts are at much earlier stages.
"We are making good progress with our research efforts in antimicrobial agents," Loar said. "We recently initiated a program for hepatitis C viral replication." It has lead compounds for the microbial efforts.
Separately Thursday, Genelabs reported its third-quarter earnings. The company posted a net loss of $4.3 million for the period, or 8 cents per share. For the first nine months of the year, it lost $12.1 million. As of Sept. 30, it had $11.5 million in cash, cash equivalents and short-term investments.