La Jolla Pharmaceutical Co. said additional positive results from aPhase II trial of its lupus drug, LJP 394, were encouraging enough toadvance the start of a Phase II/III study originally scheduled to beginearly next year.
Andrew Wiseman, director of business development for San Diego-based La Jolla Pharmaceutical, said the late-stage study, which willevaluate the drug's ability to slow progression of lupus nephritis, willbegin by the end of December 1996.
If the Phase II/III demonstrates LJP 394's safety and effectiveness,FDA officials have suggested La Jolla Pharmaceutical may be able tofile for market approval based on that one study, rather than waitingfor confirmatory results from a second Phase III trial.
Data from the Phase II/III trial are expected in about two years fromthe start of the study.
The new timetable, Wiseman observed, was made possible by PhaseII findings showing treatment with LJP 394 resulted not only inreduction of disease-causing antibodies linked to lupus nephritis, butthe patients also experienced an increase, or normalization, in levelsof two complement proteins, called C3 and C4.
The latter markers provided more evidence the drug preventedproduction of the targeted antibodies. Complement proteins, part ofthe immune response promoting inflammation, are activated by thedisease-causing antibodies and then destroyed, reducing levels of theproteins below normal.
LJP 394 is a molecule, created with La Jolla Pharmaceutical'sTolerance Technology, designed to bind to the surface of B cells andto shut off their production of double-stranded DNA antibodies,which attack kidneys. Damage to the kidneys is the main killer oflupus patients.
Interim data from the Phase II trial, presented in February 1996,showed the lupus drug was safe and that levels of the double-strandedDNA antibodies decreased as LJP 394 dosage increased. (SeeBioWorld Today, Feb. 19, 1996, p. 2.)
The additional Phase II data were released this week and showedpatients receiving 50 mg of the drug once a week experienced a 48percent decrease in median levels of double-stranded DNAantibodies as well as increases in C3 proteins of 15 percent and C4proteins of 9 percent.
La Jolla Pharmaceutical said the findings also demonstrated LJP 394achieved statistical significance compared to the placebo in reducingantibody levels in patients receiving 50 mg or 10 mg once a week.
The Phase II study involved 58 patients. Nine were in the placebogroup and the other 49 were divided into 9 treatment groupsreceiving either 1 mg, 10 mg or 50 mg of LJP 394, once a week, onceevery two weeks or once every four weeks.
La Jolla Pharmaceutical had planned to conduct a Phase IIb trial topinpoint dosage and add to the evidence of efficacy prior to the PhaseII/III study.
Instead the company will proceed directly to the late-stage trial with300 patients divided into two groups, half receiving a placebo and theother taking 100 mg of LJP 394 once a week for 12 months.Following treatment, the patients will be monitored for six monthsbefore data are compiled. During the trial, investigators also willdetermine the best mix of dose and frequency to first reduceantibodies and then maintain those levels.
LJP 394 is not considered a cure. The drug is designed to stabilizethe loss of kidney function in lupus patients.
The main endpoint for the Phase II/III study is an evaluation of thetime it takes patients to progress to renal flare, an indication thedisease is worsening. Renal flare normally is treated with high-dosesteroids and cyclophosphamide, both of which suppress the immunesystem and cause a variety of adverse side effects.
Wiseman said 35 to 40 percent of the patients in the placebo groupare expected to progress to renal flare during the Phase II/III study.
Lupus patients in the trial also will be taking low-dose steroids, astandard therapy for the disease, and the study also will examine LJP394's ability to reduce reliance on those drugs.
La Jolla Pharmaceutical's stock (NASDAQ:LJPC) closed Tuesday at$3.937, down $0.188. n
-- Charles Craig
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