By Mary Welch

La Jolla Pharmaceutical Co. laid off 43 percent of its staff, or 41 employees, as a result of Abbott Laboratories' decision to withdraw its developmental support of LJP 394, following the stoppage in May of a Phase II/III trial for lupus nephritis.

"Abbott terminated the agreement after they and an independent third party reviewed the data and found it supported the opinion of the independent data monitoring committee - namely that LJP 394 did not achieve statistical significance," said Richard Krawiec, vice president of investor relations for San Diego-based La Jolla.

As a result of Abbott's action, La Jolla cut its work force from 95 to 54, with all departments being affected, he said. "We have $17.8 million in cash as of June 30, and we expect that will last us to the end of 2000. The layoffs will result in substantial savings."

La Jolla and Abbott, of Abbott Park, Ill., started their collaboration in 1996, with Abbott pledging at least $50 million to La Jolla, including an up-front payment of about $10 million. It is believed Abbott paid at least $50 million, including development costs, in the collaboration. (See BioWorld Today, Dec. 27, 1996, p. 1.)

La Jolla, while continuing to review LJP 394, will now concentrate on developing an experimental drug for the treatment of stroke, heart attack and deep-vein thrombosis, Krawiec said.

LJP 394 is based on the company's Toleragen technology and, given intravenously, is designed to reduce the levels of the auto-antibodies to double-stranded DNA that are believe to promote lupus kidney disease. Specifically, the molecule is designed to suppress the production of the renegade B cells responsible for making pathogenic antibodies, without suppressing the entire immune system.

The LJP 394 molecule comprises four double-stranded deoxyribonucleotide strands conjugated to a triethylene glycol platform, designed to cross-link B-cell receptors, thus sending a signal that shuts down antibody production.

The compound is designed to bind to the surface of cells and stop their production of double-stranded DNA antibodies, which attack the kidneys. Damage to the kidneys is the major killer of lupus patients. There are about 500,000 lupus patients in the U.S., with 16,000 new cases diagnosed each year.

Toleragens are composed of multiple copies of B cell epitopes attached to a nonimmunogenic carrier platform. The same basic carrier platform can be used with different epitopes to make a variety of Toleragens to treat various autoimmune diseases, the company said.

The trial's primary endpoint was the prevention or delay of life-threatening renal flares. Secondary endpoints were reducing disease activity, permitting lower doses of steroids and chemotherapy, and improving overall quality of life.

"What is interesting is that LJP 394 did statistically significantly reduce antibody levels in two trials - one by 45 percent and the other by 50 percent," Krawiec said. "In other words, in patients receiving LJP 394, circulating antibodies to double-stranded DNA were reduced. We're still trying to figure out what happened. We still believe it supports the validity of our Toleragen technology but we we're still trying to figure out why it didn't have a greater efficacy in the primary endpoint. We're still studying it."

La Jolla's stock (NASDAQ:LJPC) closed Wednesday at 59.38 cents per share, down 6.25 cents.