By Kim Coghill
Using lessons learned from disappointing results of its Phase II/III trial, La Jolla Pharmaceutical Co. said Wednesday that it has initiated a Phase III clinical trial of its lupus drug, LJP 394.
The drug is intended to reduce levels of antibodies to double-stranded DNA, which are believed to be responsible for lupus kidney disease. The pivotal Phase III trial is expected to last two years and is designed to confirm the positive results from the Phase II/III trial for patients with high-affinity antibodies to LJP 394, said Steven Engle, chairman and CEO of San Diego-based La Jolla Pharmaceutical.
Engle said the Phase III will be different from the last trial in that participants will receive weekly 100-mg doses of the drug as opposed to taking 50-mg doses "on and off." The Phase II/III study enrolled more than 200 patients who were treated up to 18 months. Results showed 89 percent of the patients had high-affinity antibodies to LJP 394 and the time to renal flare - the endpoint of the trial - in high-affinity patients was significantly increased. (See BioWorld Today, May 4, 2000, p. 1; and Feb. 17, 2000, p. 4.)
But in the earlier trial, La Jolla failed to meet its endpoints, causing partner Abbott Laboratories, of Abbott Park, Ill., to withdraw from development support. Regarding partnership for Phase III, Engle said, "We are pursuing conversations with other companies, but we have not decided whether we will have a corporate partnership."
The current trial - named PEARL, or Program Enabling Antibody Reduction in Lupus - has the same endpoints as the Phase II/III trial and likely will have some of the same participants, Engle said.
The double-blind, placebo-controlled trial set to be conducted at 75 medical centers in North America and Europe will involve 300 lupus patients with a history of kidney disease. The efficacy analysis will focus on patients with high-affinity antibodies for LJP 394. Also, the drug will be evaluated to determine whether it prevents or delays renal flares, reduces the need for treatment with high-dose corticosteroids or chemotherapy drugs, and improves quality of life.
"Most lupus patients need high doses of steroids or chemotherapy drugs, which end up causing side effects," Engle said. "In many patients, the common cold can send them to the hospital. We want to reduce these events and our last trial showed one-third as many renal flares.
"I don't know if we'll eliminate side effects, but they will drop," he said.
High doses of corticosteroids and chemotherapy drugs have increased the survival rate, but the toxic effects of these drugs have attributed to morbidity and mortality in lupus.
Lupus is an autoimmune disease with few treatment options and little or no innovation in treatment for decades. It is a chronic, life-threatening disease most commonly affecting women. The onset is usually during childbearing years. In lupus, antibodies to double-stranded DNA are believed to be responsible for potentially severe and often progressive kidney disease that can lead to kidney failure and the need for dialysis or kidney transplantation.
La Jolla's stock (NASDAQ:LJPC) gained 50 cents, or 6 percent, Wednesday to close at $9.