Associate Managing Editor

Amid ongoing discussions with the FDA, La Jolla Pharmaceuticals Co. is pushing ahead with the filing of a new drug application for its lupus drug, Riquent, with - for now, anyway - data from two trials that missed primary endpoints but showed positive trends.

"We met with the FDA and they have indicated that we can go ahead and file the NDA," Steve Engle, CEO and chairman of La Jolla, told BioWorld Today, adding that the discussion with the agency is ongoing. "We recognized that the two trials are two of the best ever run. Based on that, we are moving ahead to prepare the NDA for submission while we are in discussions."

In February, the news of the failed Phase III trial devalued La Jolla's stock (NASDAQ:LJPC) 72.5 percent, leaving it trading just above the $2 range. It sank as low as $1.14 in March before beginning to climb. On the news of the intended filing Monday, it jumped 55 cents, or 26.8 percent, to close at $2.60.

Without a successful pivotal trial, it would appear the deck is stacked against a Riquent approval. But what the drug and La Jolla, of San Diego, have going for them is a demonstrated drop in antibodies to double-stranded DNA in both trials and a lupus population desperately in need of treatments. In March, La Jolla released analyses of data from the Phase III and Phase II/III studies that showed statistically significant correlations between reductions in antibodies to double-stranded DNA and a reduced risk of renal flare in lupus patients (Phase III: p<0.0001; Phase II/III: p=0.0004). Also, it said the Phase III results demonstrated that Riquent lowers levels of antibodies to dsDNA in a statistically significant manner (p<0.0001)

And then there are the patients.

"It's urgent. It's critical," said Sandra Raymond, CEO and president of the Lupus Foundation of America, referring to the necessity for new lupus drugs. "You have to talk to these patients to understand how critical the need is. There hasn't been a new drug for lupus for 30 years."

Although there are "a host of treatments," Raymond said, such as corticosteroids and chemotherapy drugs, "many of them are toxic and cause serious side effects that exacerbate the conditions of the patients."

Riquent might be able to step into that void. Although unable to show in the Phase III trial a statistically significant increase in time to renal flare, the primary endpoint in both the Phase III and the Phase II/III trials, Riquent's ability to reduce antibodies to double-stranded DNA might mean the drug could provide benefit. (See BioWorld Today, May 14, 1999, and Feb. 19, 2003.)

However, a reduction of antibodies has not been the primary endpoint of a Riquent pivotal trial, something the FDA usually wants. So while Engle said, "I think that people are convinced that the drug does one thing well, which is lower the antibodies," he acknowledged that until the discussions with the FDA are complete, it's "hard to know what to say" about the path ahead and added that La Jolla was prepared for the stipulation that "there might be other supporting data and trials required."

Riquent, formerly called LJP 394, has orphan drug status in both the U.S. and Europe. La Jolla plans to take the same package of data it took to the FDA across the Atlantic to regulatory authorities there for similar discussions. If all goes well in the States, La Jolla expects to finish the application around the end of 2003, although it hopes to hear from the FDA what, if anything, more is required before then.

When the product hit the Phase II/III snag, Abbott Laboratories, of Abbott Park, Ill., pulled out of the companies' partnership. La Jolla owns all rights to the drug today. Although not commenting on partnering, Engle did say the company has "had interest" - even before news of the NDA. (See BioWorld Today, Sept. 16, 1999.)

La Jolla has not geared up for a launch and in fact has been "closely managing" its costs since the failed Phase III trial. It ended the year with $52.7 million in cash and has a $125 million shelf registration active. Engle said that "once the regulatory pathway is clear, we'll know which way to go," regarding any partnering or marketing plans.

For now, though, La Jolla moves ahead with its filing. There are other potential treatments out there - Genelabs Technologies Inc., of Redwood City, Calif., received an approvable letter for its product, Prestara, contingent on a confirmatory trial; and Human Genome Sciences Inc., of Rockville, Md., has LymphoStat-B in early clinical development, for instance - but La Jolla has given the lupus community a reason to be optimistic.

"We remain very hopeful," Raymond told BioWorld Today. "We saw the [Phase III data] and we think they are promising. We hope the FDA will make a decision soon."