Forging ahead with its lupus drug, Prestara, Genelabs Technologies Inc. has decided to conduct another Phase III trial, and likely will look for a development partner to help offset costs.

During a recent meeting with the FDA, the agency told Genelabs that an additional pivotal trial would be needed to support the drug's approval as a treatment for the signs and symptoms of systemic lupus erythematosus. At the same time, the company decided not to pursue Prestara in the prevention of bone mineral density loss in lupus patients, despite receiving an approvable letter for that indication in 2002, based on results from a nested Phase III study showing that patients receiving Prestara had increased mean bone mineral density (BMD) of the lumbar spine and hip compared to decreased BMD in the placebo group. (See BioWorld Today, Sept. 3, 2002.)

"We went down that road because it looked like a quicker path to approval," said Matthew Loar, chief financial officer of Redwood City, Calif.-based Genelabs.

But that road proved to be a bumpy one. In October 2004, the company reported disappointing results from its intended confirmatory trial of Prestara, which missed its primary endpoint in demonstrating increased bone mineral density at a statistically significant rate over placebo. Another trial, involving 155 patients and conducted in Taiwan, also failed to show a significant increase in BMD in lupus patients. (See BioWorld Today, Oct. 6, 2004, and April 8, 2005.)

"With the latest trials not showing statistical significance, and the meeting we just had with the FDA, we decided we're going after signs and symptoms of lupus rather than the bone indication," Loar told BioWorld Today. "And certainly with lupus, we think it's better to treat the disease than to just treat the bones of the patients."

Lupus, a disease that affects mostly women and characterized by a range of symptoms associated with inflammation and organ damage, typically is treated with glucocortoids, which can produce side effects such as bone loss, infection and accelerated atherosclerosis. No new treatments have been approved in the past 40 years, a fact that's not surprising given the difficulties that Genelabs and other companies have encountered while trying to get products through clinical testing.

San Diego-based La Jolla Pharmaceuticals Co. was asked to conduct an additional Phase III trial after receiving an approvable letter in 2004 for its Riquent (abetimus sodium), and later learned its drug was unlikely to get accelerated approval, forcing the company to lay off about 60 employees. La Jolla later closed a $66 million financing to help fund the trial. (See BioWorld Today, Oct. 11, 2005.)

Human Genome Sciences Inc., of Rockville, Md., is planning to enter its first Phase III study this year, despite mixed data from a Phase II trial with its lupus antibody drug, LymphoStat-B (belimumab). HGS and partner London-based GlaxoSmithKline plc reported in October that the drug missed its overall endpoint, but showed a statistically significant reduction in lupus signs and symptoms in a subgroup of seropositive patients. (See BioWorld Today, Oct. 6, 2005.)

"It's a tough indication for everybody," Loar said.

Genelabs' Prestara was developed as a pharmaceutical preparation containing prasterone, a synthetic form of the human hormone dehydroepiandrosterone, as its active ingredient. The company also might pursue expanded indications for the product, but not until it gains approval in lupus.

Right now, Genelabs' next steps will be to design the new pivotal trial, with concurrence from the FDA, and "after that point, we'll be able to put a better timeline on it," Loar said.

In the meantime, the company plans to seek help from a new or existing partner. Genelabs licensed in November 2000 North American rights to Corona, Calif.-based Watson Pharmaceuticals Inc., in a deal that could carry "a significant royalty" payment and up to $45 million in milestones to Genelabs upon the product's approval, Loar said, but getting it to the market "is pretty much our responsibility, and we don't have sufficient funds to pay for this trial ourselves."

Genelabs has partnered out rights to Prestara in Japan to Osaka, Japan-based Tanabe Seiyaku Co. Ltd. The company has not yet signed a European collaborator.

While Prestara is the most advanced drug in its pipeline, Genelabs is focusing much of its efforts on its preclinical hepatitis C programs. Among those is a collaboration with Foster City, Calif.-based Gilead Sciences Inc. involving nucleoside inhibitors of HCV polymerase. The deal, signed in 2004, could result in payments of up to $46 million if a compound is commercialized. (See BioWorld Today, Oct. 1, 2004.)

Genelabs also has an ongoing collaboration with GlaxoSmithKline for a hepatitis E vaccine, which recently demonstrated positive results in a Phase II study.

The company reported a net loss of $2.8 million, or 3 cents per share, for the third quarter. As of Sept. 30, it had a cash position of $14.4 million.

Shares of Genelabs (NASDAQ:GNLB) gained 6 cents Friday to close at $1.85.