LJP 1082
SAN DIEGO, Oct. 27 /PRNewswire-FirstCall/ -- La Jolla Pharmaceutical Company (Nasdaq: LJPC - News) announced preliminary results from the first clinical trial evaluating its experimental drug candidate, LJP 1082, for the treatment of antibody-mediated stroke, heart attack, deep vein thrombosis and recurrent miscarriage. The Phase I/II trial was a randomized, placebo-controlled study that was designed to evaluate the safety and activity of a single dose of LJP 1082. Based on an initial assessment of the trial data, the drug was well tolerated at all five dose levels. LJP 1082 had an elimination half-life of at least 12 hours following intravenous administration.
LJP 1082 is designed to reduce antibodies to the first domain of beta 2 glycoprotein 1 (beta 2 GP1) that are believed to promote antibody-mediated thrombosis. LJP 1082 is composed of four copies of the first domain of beta 2 GP1 coupled to a synthetic chemical platform. Following treatment with a single 50 mg or 200 mg dose, antibodies to LJP 1082 were reduced in some patients. In total, 20 patients with a history of antibody-mediated thrombosis participated in the trial period.
Standard safety assessments including physical exams, lab values and vital signs, and immunology specific measurements were taken over 30 days following a single dose of LJP 1082. All adverse events observed were categorized as mild to moderate and deemed to have no or an unlikely relationship to study drug. The adverse event profiles appeared similar between drug-treated and placebo-treated groups. There were no serious adverse events. No significant increase in circulating immune complexes, changes in complement protein C3 or activation of patient T cells was observed following drug treatment.
Even though there were a small number of patients in the study, there was an apparent dose-dependant response following drug treatment. Patients receiving higher doses of LJP 1082 had larger reductions in antibodies to LJP 1082. In the 50 and 200 mg treatment groups, there was an apparent correlation between the level of reduction and the affinity of the patient's antibodies for drug. Most patients had antibodies that were specific for the first domain of the target protein, beta 2 GP1, which is the epitope presented on LJP 1082.
This study is the first of several that may be required to establish appropriate dose regimens and the observed reductions may not be large enough to affect patient health or reduce antibodies to beta 2 GP1in a majority of patients. Additional analyses are ongoing. Potential drug interference in some of the antibody assays is also being evaluated. This study was not designed to evaluate the ability of LJP 1082 to tolerize B cells that produce antibodies to beta 2 GP1 and additional studies will be needed.
These findings were presented today at the American College of Rheumatology Annual Meeting currently being held in New Orleans. Matthew Linnik, Ph.D., Chief Scientific Officer and Executive Vice President of Research at La Jolla Pharmaceutical presented the poster entitled "A Novel Therapeutic Approach for Treating Antiphospholipid Syndrome Based on Tolerizing anti-beta 2 glycoprotein 1 B cells".
Design of Phase I/II trial for LJP 1082
In the Phase I/II trial, five different groups, each consisting of four or five patients, were treated with a single intravenous dose of LJP 1082 of 1, 3, 10, 50 or 200 mg and then monitored for 30 days. One patient in each group received placebo. In order to participate in the trial, patients were required to have elevated levels of antibodies to beta 2 GP1, the target of the antibodies involved in antibody-mediated thrombosis.
"LJP 1082 is designed to specifically prevent the production of disease-causing antibodies, while leaving the rest of the immune system fully functional and without the increased risk of bleeding episodes associated with existing anticoagulant therapy," said Dr. Linnik.
Antibody-Mediated Thrombosis
Antibody-mediated thrombosis is an autoimmune disease characterized by the formation of blood clots that lead to stroke, heart attack, deep vein thrombosis and recurrent miscarriage. This disease, also know as Antiphospholipid Syndrome, affects an estimated one to two million people in the United States and Europe. Patients often experience their first thrombotic event in their 20s or 30s, and studies indicate they have twice the probability of a recurrence. Current treatments include anticoagulants, the long-term use of which can lead to side effects including life-threatening bleeding events. LJP 1082 is the first drug candidate specifically designed to treat the underlying cause of antibody-mediated thrombosis... |
