Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Abetimus [Abetimus sodium, LJP 394, Rentol, Riquent] is a synthetic Toleragen molecule consisting of four double-stranded oligodeoxyribonucleotides attached to nonimmunogenic polyethylene glycol, a proprietary carrier platform. It was originated by La Jolla Pharmaceuticals. Abetimus is an immunomodulating agent that induces tolerance in B cells directed against double-stranded DNA (dsDNA). It does this by cross-linking surface antibodies. These antibodies are thought to be responsible for lupus nephritis, a chronic kidney disease that develops in patients with systemic lupus erythematosus. A phase III trial of abetimus was completed in December 2002. La Jolla Pharmaceuticals previously established two licensing agreements for abetimus, which have since been terminated. One of the agreements was with Leo Pharmaceutical Products of Denmark. The company was licensed rights to abetimus covering Europe and the Middle East. The other agreement was with Abbott Laboratories. Abbott returned all rights to abetimus to La Jolla Pharmaceuticals in September 1999 based on the results of an analysis of the phase II/III trial of abetimus in lupus patients with a history of renal disease. A phase III trial, named "PEARL" (Program Enabling Antibody Reduction in Lupus), has been conducted in the US in patients with lupus nephritis. It enrolled 317 patients with a history of lupus who were treated with a weekly dose of abetimus 100mg or placebo. The trial was completed in December 2002 and preliminary results were reported in February 2003. PEARL was designed to determine whether abetimus can significantly delay renal flares and delay the need for treatment with high-dose corticosteroids and/or cyclophosphamide in patients with high affinity IgG antibodies to the double-stranded oligonucleotide epitope in abetimus. Patients with high-affinity antibodies, were selected using a surface plasmon resonance (SPR)-based pharmacoproteonomics assay provided by Biacor International. Following the completion of PEARL in December 2002, La Jolla Pharmaceuticals initiated an on-going, open-label, follow-on trial. All patients who had completed PEARL were eligible to enroll and receive weekly treatment with abetimus. However, in April 2003, La Jolla Pharmaceuticals announced that it was closing this trial, which was designed to collect additional long-term safety data, to conserve resources for the continued development of the drug. Previously, La Jolla Pharmaceuticals and Abbott initiated a phase II/III trial of abetimus in more than 200 patients with lupus nephritis. However, this trial was discontinued in May 1999 because the primary end-point (time to renal flare) was much shorter than expected. After the trial was halted, further analysis of trial data using a new blood test to measure the strength of the binding between abetimus and a patient's antibodies to dsDNA was conducted. The additional analysis showed that the number of renal flares in the high-affinity patients (responders) treated with abetimus was less than half of the number of renal flares in high-affinity patients treated with placebo. Responders also showed a significant reduction in the use of high-dose corticosteroids and cyclophosphamide. Being able to screen patients to identify those likely to respond to therapy lead La Jolla Pharmaceuticals to initiate PEARL after Abbott's withdrawal from the drug. It is believed that screening patients will help increase the cost-effectiveness of clinical development. In September 2000, the US FDA granted orphan drug status for abetimus in the treatment of lupus nephritis. The European Commission followed suit in November 2001, granting orphan drug status for abetimus in the EU.
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PMID:Abetimus: Abetimus sodium, LJP 394. 1274 59

Abetimus sodium has been under development for the treatment of systemic lupus erythematosus since the early 1990s. Because its administration results in the selective reduction of circulating double-stranded DNA antibodies, La Jolla Pharmaceutical Company has focused on the agent's ability to prolong time to nephritic flare. Fourteen trials have been initiated since 1994, but the two pivotal registration trials failed to meet primary end points. The US Food and Drug Administration issued a letter in October 2004 that stated abetimus sodium was "approvable" pending the successful completion of a trial demonstrating clinical benefit. The fate of this agent lies in the ability of the company to successfully complete a phase III study.
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PMID:Abetimus sodium (riquent) for the prevention of nephritic flares in patients with systemic lupus erythematosus. 1650 27

Lupus nephritis (LN) is a major cause of morbidity and mortality, affecting over half of SLE patients. The traditional treatment protocol with cyclophosphamide and corticosteroids dramatically improved patient and renal survival, but conferred a heavy burden of side effects. In addition, not all patients respond to first-line immunosuppression; 35% suffer at least one episode of renal relapse and 5-20% develop end-stage renal disease. Over the last decade, the increasing understanding of the complex pathogenesis underlying lupus nephritis and accelerating advances in molecular and cellular immunology have paved the way for development of immunomodulatory therapies for LN. In contrast to the global immunosuppressive effects of conventional treatment, these biologic agents target specific pathways that contribute to the inflammatory response, aiming to reduce tissue damage while preserving immunocompetence. The goal of this review is to highlight some of the more promising novel immunomodulators, including Abetimus sodium, Rituximab, Epratuzumab, Abatacept, Belimumab, Tocilizumab and Infliximab, and discuss how these agents affect central pathways in the pathogenesis of disease.
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PMID:Treatment of lupus nephritis: facing the era of immunotherapy. 1892 28