By Karen Pihl-Carey
Genelabs Technologies Inc. reported a second Phase III trial of GL701 demonstrated positive results that will lead to the filing of a new drug application as a treatment for systemic lupus erythematosus (SLE).
If approved, GL701 would be the first new treatment for SLE in 40 years.
The company would not say yet whether the drug reached statistical significance.
"We haven't released data at this point. We expect to put it in public domain before submitting the NDA," Genelabs president James Smith told BioWorld Today. "But the results of the trial are positive, sufficiently so that we're planning to go ahead with an NDA submission."
Genelabs' stock (NASDAQ:GNLB) closed Tuesday at $3.281, up 59.38 cents, or 22 percent. The company had 39.8 million outstanding shares as of June 30.
The random study initiated in March 1996 focused on 381 women with SLE who received either an oral dose of 200 mg of GL701 or placebo once a day for a year.
The primary endpoint was to determine whether the drug could improve or stabilize clinical outcome and disease symptoms in SLE patients. Among the efficacy measurements were the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), the Systemic Lupus Activity Measure, the Krupp Fatigue Severity Score and the Patient Global Assessment.
Genelabs, of Redwood City, Calif., initiated the first Phase III trial of GL701 in May 1994. Earlier this year, the FDA gave the drug fast-track status, meaning the agency has six months to make a decision either way upon receipt of the NDA. The drug also has received orphan drug designation, giving Genelabs seven years of marketing exclusivity "for any product that contains the same active ingredient for the same indication," Smith said.
The company has not speculated as to when GL701 could be on the market, but Genelabs has requested a pre-NDA meeting with the FDA and the submission process would be expected to begin immediately following the meeting.
"It's our intention to seek licensees outside the U.S. We have no intention of building infrastructure outside the U.S. to develop the product," Smith said. Within the U.S., the company plans to retain its right to market the drug, deploying a sales force of no more than 15 people. It would market mostly to rheumatologists, the specialists who treat patients with SLE. The company has not determined a price for the drug yet.
"There's been no new drug to treat lupus in the past 40 years," Smith said. "As a consequence, there's nobody promoting in that sector. It's a fairly reachable audience. We have been approached by some other companies that have expressed interest and we'll continue in those discussions, but at this point it seems wise to introduce the product ourselves."
Genelabs contracted two years ago with Schering-Plough Corp., of Madison, N.J., to manufacture GL701. The company will need to raise more money in order to market the drug. As of June 30, Genelabs had $13.5 million in cash.
"We expect that we'll need to raise additional capital before the end of 2000," Smith said. "To build the infrastructure [to market the drug] we would need to do so."
SLE affects an estimated 1 million people worldwide, 200,000 in the U.S., and mostly women. The onset of the disease occurs in the late teens and early 20s with symptoms such as severe fatigue, arthritis, facial rash, unusual sensitivity to sunlight and inflammation of the lungs and heart. It causes the immune system to attack the body's own tissue. In serious situations, the disease causes the life-threatening inflammation of the brain tissue, as well as kidney failure. There is no cure, and the current treatment is limited to the continuous use of steroids such as prednisone.
In 1993, Genelabs attained exclusive worldwide marketing and sublicensing rights to GL701 from Stanford University. Under the agreement, the university would receive milestone and royalty payments based on clinical development goals and sales figures. (See BioWorld Today, Nov. 12, 1993, p. 1.)
The drug's therapeutic approach is to increase levels of dehydroepiandrosterone (DHEA), a naturally occurring hormone produced by the adrenal glands. GL701 contains prasterone, the generic designation for DHEA, as its active ingredient. People with SLE typically have abnormally low levels of DHEA.
In the first Phase III trial, which was a double-blind, randomized, placebo-controlled study, GL701 was tested in 191 women. They received daily treatments over seven to nine months of either 100 mg of the drug, 200 mg of the drug or a placebo. They were also taking 10 to 30 mg daily of prednisone, which has side effects, such as premature osteoporosis, atherosclerosis and diabetes. The study's endpoint was the reduction of the prednisone dose to 7.5 mg daily or less for at least two months, while the disease activity either stabilizes or improves. About half of the patients with mild to moderate lupus who received the 200 mg dose achieved the primary endpoint, compared with 29 percent of placebo patients. (See BioWorld Today, Nov. 13, 1997, p. 1.)
Aside from its work with GL701, the company is studying DNA-binding drugs for cancers and autoimmune disease, as well as RNA-binding drugs for broad spectrum antivirals.
Genelabs has a $13.6 million grant for three years from the Defense Advanced Research Projects Agency, a part of the U.S. Department of Defense, to create a database that will help the rapid design of drugs to counter pathogens employed in biological warfare. Through a collaboration with SmithKline Beecham, of London, the company is developing a system for regulating expression of genes needed for survival or replication of certain bacteria. Genelabs also is collaborating with DuPont Pharmaceutical Co., of Wilmington, Del., to develop small-molecule gene-regulating drugs. The goal of both collaborations is to discover lead compounds that could become products generating royalties for Genelabs.