La Jolla Pharmaceutical Company (NASDAQ:LJPC) today announced positive
12-month interim antibody data from its ongoing double-blind,
placebo-controlled, randomized Phase 3 study of Riquent®
(abetimus sodium), its drug candidate for systemic lupus erythematosus ("SLE”
or "lupus”).
Analyses of 12-month interim antibody data in the first 125 patients
randomized in the study indicate that for all patients treated with 900
mg, 300 mg, or 100 mg of Riquent per week compared with placebo, there
were significantly greater reductions in antibodies to double-stranded
DNA (dsDNA, p < 0.0001).
Summary of Antibody Data
The data show a dose-response curve for antibody reduction and also show
that the 300 mg and 900 mg doses appear to be near the top of the
antibody-related dose-response curve, thus supporting the choice of
doses for this study. Antibody levels in the placebo-treated group
remained around baseline levels throughout the 12 months. The rate at
which antibody levels were maximally reduced appeared to be more rapid
in the 900 mg dose group than in the 300 mg or the 100 mg dose groups.
"Treatment with all doses of Riquent resulted
in significant and sustained reductions in antibodies to dsDNA during
the entire one-year treatment period,” said
Michael Tansey, M.D., Executive Vice President and Chief Medical Officer
of La Jolla Pharmaceutical Company. "Equally
important, antibody levels observed in the placebo-treated patients
remained around or above baseline and did not drift lower over time as
occurred in the previous Phase 3 study. These data, which were generated
in patients already receiving background immunosuppressive therapy,
suggest that the appropriate doses were chosen for the current study and
that overall, the 300 mg and 900 mg doses appear to be more effective
than the 100 mg dose in the sustained reduction of antibodies to dsDNA.” "The 12-month interim antibody data confirm
that over the dose range being studied, treatment with Riquent resulted
in significant reductions in antibodies to dsDNA,”
said Richard Furie, M.D., Chief of Rheumatology, North Shore-Long Island
Jewish Health System, and an investigator in the study. "These
antibodies are strongly implicated as a primary cause of lupus renal
disease, and prior studies have demonstrated that reductions in these
antibodies strongly correlate with a reduction in the risk of renal
flare.”
Each individual dose group was significantly different from placebo (p <
0.0001). An area under the curve (AUC) analysis, which reflects the
effect of the drug on antibody levels over time, showed significantly
greater antibody-lowering effects for the 300 mg and 900 mg dose groups
compared with the placebo group (decreases of 26.9% for 100 mg, 35.5%
for 300 mg, and 37.7% for 900 mg, compared with an increase of 7.5% for
placebo).
The AUC analysis provides additional evidence that the higher doses of
Riquent suppressed antibodies further than the 100 mg dose group. The
proportion of patients achieving a 50% or greater AUC reduction was 0.0%
in the placebo and 100 mg groups, 23% in the 300 mg group, and 30% in
the 900 mg group.
The 12-month antibody analysis assessed the impact of treatment with
Riquent or placebo on antibodies to dsDNA. Antibody levels were measured
every two weeks for the first 16 weeks of the study and then monthly for
the remaining 36 weeks. All demographics and baseline characteristics
were comparable across dosing groups.
Phase 3 Trial Update
The Phase 3 ASPEN trial ("Abetimus
Sodium in Patients
with a History of Lupus Nephritis”)
appears to be progressing well; more than 140 sites are active and more
than 670 patients have been enrolled. Compliance with weekly visits has
been high and the drop-out rate remains low. The Independent Data
Monitoring Board (DMB) has completed three reviews of the safety data
and has not indicated any safety issues.
The study is an event-driven trial designed to be completed when 128
renal flares have occurred. The current overall renal flare rate is
lower than the original trial assumption. As a result, in an effort to
shorten the time to achieve the required number of renal flares, the
Company will continue enrollment beyond the initially targeted 740
patients and extend the treatment period beyond 12 months until the
required number of renal flares is achieved. The Company now estimates
that at least 800 patients will be enrolled in the study. Based on these
changes, the Company expects the trial to complete in the second half of
2009.
The Phase 3 trial includes two interim efficacy analyses, each with
target p values of p < 0.001 and a final p
value of p < 0.05. The Company has added a
futility analysis to each interim efficacy analysis. The interim
efficacy analyses have been moved to occur later in the study when a
greater number of renal flares will have been observed. As a result, the
first interim efficacy analysis is expected to occur around the fourth
quarter of 2008, and the second interim efficacy analysis is expected to
occur about midway between the first analysis and the expected end of
the study.
These modifications to the trial have been discussed with the FDA, and
the trial continues to be conducted under the FDA’s
Special Protocol Assessment.
"The interim results from the ASPEN trial are
very encouraging,” said Deirdre Gillespie
M.D., President and CEO of La Jolla Pharmaceutical Company. "At
this point in the trial enrollment remains strong, the overall renal
flare rate is lower than the original trial assumption, and the safety
data appear to be consistent with data from our previous trials. These
new data appear to show that the 300 mg and 900 mg doses of Riquent
reduce antibodies to dsDNA more than the previously studied 100 mg dose.”
Dr. Gillespie added, "We continue to make
great progress and believe that the additional refinements to the study
will hasten its completion and possibly enable us to observe a
definitive outcome earlier.” Conference Call
The Company will host a conference call on April 23, 2008, at 1:30 pm
Pacific Time/4:30 pm Eastern Time. If you would like to listen to the
conference call, please access the link on La Jolla Pharmaceutical
Company’s Web site at www.ljpc.com.
A replay of the conference call will be available the day of the call on
the Company’s Web site www.ljpc.com
and will be archived for several weeks. In addition, a replay of the
conference call can be accessed by dialing 888-286-8010 (US) or
617-801-6888 (international). The passcode for the replay is 78768082.
Phase 3 Study Design
The Phase 3 study is designed to assess the ability of Riquent treatment
to prevent or delay the time to renal flare in lupus patients with a
history of renal disease and with antibodies to dsDNA. Equal numbers of
patients are being treated with 300 mg per week, 900 mg per week, or
placebo. A small number of patients are receiving 100 mg per week. All
patients continue to receive standard of care which can include
background immunosuppressive therapies.
A lupus renal flare is a potentially life-threatening increase in
inflammation of the kidney due to lupus. A renal flare often requires
treatment with immunosuppressive agents which can have severe side
effects. Riquent is also being studied to assess whether drug treatment
decreases proteinuria, as was observed in previous clinical trials.
Proteinuria, or protein in the urine, is a common problem for patients
with renal disease and is an indicator of renal damage.
Riquent has received an Approvable Letter and Fast Track status from the
Food and Drug Administration, and has Orphan Drug designation in the
United States and Europe.
About Riquent
Riquent is being developed to specifically treat lupus renal disease by
preventing or delaying renal flares, a leading cause of sickness and
death in lupus patients. It is also being studied to assess whether
Riquent treatment improves proteinuria, as was observed in previous
clinical trials. Proteinuria is an indicator of abnormal renal function.
Riquent has been well tolerated in all 14 clinical trials, with no
overall difference in the adverse event profiles for Riquent-treated
patients compared with placebo-treated patients. Riquent specifically
reduces circulating levels of anti-dsDNA antibodies and is also designed
to specifically suppress the B cells that make these antibodies.
Decreases in these antibodies are believed to be associated with a
decreased risk of renal flare. Although clinical benefit has not yet
been proven, Riquent treatment has significantly reduced these antibody
levels in all clinical trials in which they were measured.
About Lupus
Lupus (systemic lupus erythematosus) is a chronic, potentially
life-threatening autoimmune disease. About 90% of lupus patients are
female, and many are diagnosed with the disease during their
childbearing years. Approximately 50% of lupus patients have renal
disease which can lead to irreversible renal damage, renal failure and
the need for dialysis, and is a leading cause of death in lupus
patients. Latinos, African Americans, and Asians face an increased risk
of serious renal disease associated with lupus. The current standard of
care for lupus renal disease often involves treatment with high doses of
corticosteroids and immunosuppressive drugs that can cause severe side
effects including diabetes, hypertension, and sterility and may leave
patients vulnerable to opportunistic infections. To date, no
lupus-specific drug has been approved in the U.S.
About La Jolla Pharmaceutical Company
La Jolla Pharmaceutical Company is dedicated to improving and preserving
human life by developing innovative pharmaceutical products. The Company’s
leading product in development is Riquent®,
which is designed to treat lupus renal disease by preventing or delaying
renal flares. Lupus renal disease is a leading cause of sickness and
death in patients with lupus. The Company has also developed potential
small molecule drug candidates to treat various other autoimmune and
inflammatory conditions. The Company's common stock is traded on The
Nasdaq Global Market under the symbol LJPC. More information about the
Company is available on its Web site: http://www.ljpc.com.
The forward-looking statements in this press release involve
significant risks, assumptions and uncertainties, and a number of
factors, both foreseen and unforeseen, could cause actual results to
differ materially from our current expectations. Forward-looking
statements include those that express a plan, belief, expectation,
estimation, anticipation, intent, contingency, future development or
similar expression. The analyses of clinical results of Riquent®
(abetimus sodium), previously known as LJP 394, our drug candidate for
the treatment of systemic lupus erythematosus (lupus), and any
other drug candidate that we may develop, including the results of any
trials or models that are ongoing or that we may initiate in the future,
could result in a finding that these drug candidates are not effective
in large patient populations, do not provide a meaningful clinical
benefit, or may reveal a potential safety issue requiring us to develop
new candidates. The analysis of the data from our previous Phase
3 trial of Riquent showed that the trial did not reach statistical
significance with respect to its primary endpoint, time to renal flare,
or with respect to its secondary endpoint, time to treatment with
high-dose corticosteroids or cyclophosphamide. The results from
our clinical trials of Riquent, including the results of any trials that
are ongoing or that we may initiate in the future, may not ultimately be
sufficient to obtain regulatory clearance to market Riquent either in
the United States or any other country, and we may be required to
conduct additional clinical studies to demonstrate the safety and
efficacy of Riquent in order to obtain marketing approval. There
can be no assurance, however, that we will have the necessary resources
to complete any current or future trials or that any such trials will
sufficiently demonstrate the safety and efficacy of Riquent. Our
ability to develop and sell our products in the future may be adversely
affected by the intellectual property rights of third parties or the
validity or enforceability of our intellectual property rights. Additional
risk factors include the uncertainty and timing of: our ability to raise
additional capital; obtaining required regulatory approvals, including
delays associated with any approvals that we may obtain; the timely
supply of drug product for clinical trials; our ability to pass all
necessary regulatory inspections; the increase in capacity of our
manufacturing capabilities for possible commercialization; successfully
marketing and selling our products; our lack of manufacturing, marketing
and sales experience; our ability to make use of the orphan drug
designation for Riquent; generating future revenue from product sales or
other sources such as collaborative relationships; future profitability;
and our dependence on patents and other proprietary rights. Accordingly,
you should not rely upon forward-looking statements as predictions of
future events. The outcome of the events described in these
forward-looking statements are subject to the risks, uncertainties and
other factors described in the "Risk Factors”
contained in our Annual Report on Form 10-K for the year ended December
31, 2007, and in other reports and registration statements that we file
with the Securities and Exchange Commission from time to time. We
expressly disclaim any intent to update forward-looking statements.
