By Karen Pihl-Carey
Despite stumbling with early Phase II/III data last year, La Jolla Pharmaceutical Co. is back on track with its lupus drug LJP 394, armed with stronger data and prepared to begin a Phase III trial in the second half of this year.
The company hit a bump last year when Abbott Laboratories, of Abbott Park, Ill., withdrew developmental support of the product following preliminary Phase II/III results that suggested the drug was unlikely to meet its primary endpoints. (See BioWorld Today, May 14, 1999, p. 1; and Sept. 16, 1999, p. 1.)
The news has since gotten better. In February, San Diego-based La Jolla said 80 percent of patients evaluated showed high-affinity antibodies to LJP 394. (See BioWorld Today, Feb. 17, 2000, p. 4.)
And now an updated analysis of more than 99 percent of North American patient samples show that 89 percent of the patients had high-affinity antibodies to LJP 394, increasing the significance of the clinical results, the company said Wednesday.
"This data is similar, except that it's stronger," said Andrew Wiseman, senior director of business development and head of investor relations at La Jolla. "The data earlier in the year was based on 60 percent to 70 percent of the patient samples. That's all we had available at the time."
The Phase II/III study enrolled 211 patients, with 106 of them in the placebo-treated group and 105 of them in the drug-treated group.
In the high-affinity subpopulation, there were 95 patients in the placebo-treated group and 91 in the drug-treated group. The primary endpoint of the trial, time to renal flare, was significantly increased in high-affinity patients taking the drug, compared with those on placebo (p=.007). And there were three times as many renal flares in placebo-treated patients as there were in drug-treated patients (p<.001).
Also, in the high-affinity subpopulation, 34 placebo-treated patients needed treatments with high-dose corticosteroids and/or cyclophosphamide, compared with 13 among the LJP 394-treated patients. In the full population, 38 placebo-treated patients received treatments with high-dose corticosteroids and/or cyclophosphamide, compared with 23 drug-treated patients.
"Because we've been able to analyze a larger population, the statistical significance of most of the endpoints has strengthened," Wiseman told BioWorld Today. "That's especially true of the renal flare endpoint. The results are stronger, the statistical significance is greater, it's more meaningful."
As a result, and following a positive meeting with the FDA, the company announced Tuesday it would begin a Phase III trial in the second half of this year. Wiseman expects the trial's primary endpoint again would be time to renal flare, but that could change, he said. The Phase III trial likely will enroll about 300 patients initially in North America and then later in Europe.
"Our expectation today is that the trial will involve a year of dosing, a 100-mg dose a week for one year," Wiseman said. "Including enrollment and all the logistics, we expect it will take two years, maybe slightly longer. And then we could move directly to filing" a new drug application. The time estimates, he said, will depend on the rate of enrollment.
LJP 394 is designed to arrest the production of antibodies to double-stranded DNA in lupus patients without suppressing the healthy functions of the immune system. Clinical trial results suggest the drug is well-tolerated.
La Jolla's stock (NASDAQ:LJPC) closed Wednesday at $4.25, up 31.25 cents.