By Mary Welch
With patient retention higher than expected, La Jolla Pharmaceutical Co. has enrolled about 200 in a Phase II/III trial of LJP 394, which, the company said, may be the largest study ever of a treatment for lupus.
The 18-month trial in 40 centers across North America is expected to end by early 2000, according to Steven Engle, chairman and CEO of San Diego-based La Jolla, who said the company is in "countdown mode" to file a new drug application with the FDA.
LJP 394, given intravenously, is designed to reduce the levels of antibodies to double-stranded DNA that are believed to promote lupus kidney disease. Specifically, it's intended to suppress the production of the renegade B cells responsible for making pathogenic antibodies, without having any broader toxic effect, such as suppressing the immune system.
"Treatment [using existing therapies] is often as bad as the disease itself," Engle said.
The LJP 394 molecule is comprised of four double-stranded deoxyribonucleotide strands conjugated to a triethyleneglycol platform, designed to cross link B-cell receptors, thus sending a signal that shuts down antibody production.
The Phase II/III trial, intended to enroll 174, aims to determine whether LJP 394 is more effective than a placebo in preventing or delaying renal flares, which can be life-threatening and may require costly hospitalization. The trial will also evaluate the ability of LJP 394 to reduce disease activity, permit lower doses of steroids and chemotherapy, and improve the overall quality of life.
"Even if this drug simply reduces the amount of steroids and chemotherapy a patient requires, that's a major benefit for the patient," Engle said.
Lupus is a chronic, lifelong, potentially fatal disease in which B cells, normally producers of disease-fighting antibodies, instead create disease-causing antibodies. The potential treatment market is estimated to be at least $1 billion. Ninety percent of lupus victims are women, and the disease generally appears between the ages of 20 and 30.
Lupus affects about 500,000 Americans, a large percentage of whom ultimately die from kidney failure. The second most common cause of death is complications arising from the use of current therapies: steroids and chemotherapy.
"Patients with severe cases have a difficult lifestyle, plus they are immune-suppressed," Engle said. "Lupus is called 'the great mimic,' because the symptoms, such as fatigue, skin rashes, low-grade fever and arthritic aches, are difficult to diagnose. It can sometimes take years to finally diagnose the problem as lupus."
La Jolla Pharmaceutical in late 1996 entered into a deal worth more than $50 million with Abbott Laboratories, of Abbott Park, Ill., which is funding the lupus drug's development. La Jolla will retain worldwide manufacturing rights, sell the drug to Abbott, receive royalties and sales incentive payments, and provide marketing assistance. (See BioWorld Today, Dec. 27, 1996, p. 1.)
If La Jolla can prove the B cells can be controlled with LJP 394, the drug may offer a major new therapeutic approach in treating other diseases caused by rebel B cells, such as antibody-mediated thrombosis, myasthenia gravis, and Rh hemolytic disease.
La Jolla's stock (NASDAQ:LJPC) closed Monday at $2.375, down $0.312. *