IngentaConnect Lightening the Lupus Load: Emerging Therapies for Systemic Lupus ...

Abstract:

Systemic lupus erythematosus (SLE) is an autoimmune disorder that mainly affects women and is characterized by chronic inflammation. A range of clinical symptoms is associated with SLE, some life-threatening and all of which substantially reduce quality of life. Although management of SLE has improved over the past few decades, this is not due to improved pharmacotherapy as no new drugs for SLE have been approved by the US FDA in over 30 years. Indeed, an unmet need for safer and more effective therapies than the anti-inflammatories and immunosuppressants currently employed is driving new drug development.Most clinical investigations are focused on targeting specific immune-mediated pathways important in pathogenesis of SLE. Compounds targeting B cells are popular, with pivotal phase III clinical trials ongoing of Rituxan^® (rituximab) from Genentech and Roche, epratazumab from Immunomedics and Riquent^® (abetimus) from La Jolla Pharmaceutical. CellCept^® (mycophenolate mofetil), a novel immunosuppressant first approved in 2000 for prevention of organ transplant rejection, is also in a pivotal phase III trial for SLE. Genelabs Technologies has investigated a hormonal approach to SLE therapy with Prestara™, an oral formulation of naturally occurring dehydroepiandrosterone. However, results from phase III trials have been equivocal and the future of Prestara is uncertain.Other promising approaches include the inhibition of T cell proliferation - Orencia^® (abatacept) from Bristol-Myers Squibb and edratide from Teva are both in phase II trials - and the potential use of histone deacetylase inhibitors to reverse epigenetic changes recently implicated in pathogenesis of SLE.

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Lightening the Lupus Load: Emerging Therapies for Systemic Lupus Erythrematosus