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Biotech / Medical : Alexion Pharmaceuticals, Inc. (ALXN) -- Ignore unavailable to you. Want to Upgrade?

To: Icebrg who wrote (272)	7/8/2003 5:18:58 PM
From: Icebrg	Read Replies (2) \| Respond to of 824

Rituximab Safe, Effective for Idiopathic Membranous Nephropathy Laurie Barclay, MD July 8, 2003 — Rituximab is surprisingly efficacious for the treatment of idiopathic membranous nephropathy (IMN), inducing remission and preventing development of end-stage renal disease (ESRD), according to the results of a one-year prospective trial published in the July issue of the Journal of the American Society of Nephrology. It also appears to be safe and more favorable than commonly used medications. "IMN is an immune-mediated disease of deposits of immunoglobulin G and complement components on the subepithelial layer of the glomerular capillary wall," write Piero Ruggenenti, from the Mario Negri Institute for Pharmacological Research in Bergamo, Italy, and colleagues. "Currently available monoclonal antibodies against the B cell surface antigen CD20 have been employed to explore whether specific inhibition of B cells may help improve the outcome of IMN and may avoid the side effects of steroids and immunosuppressants." Eight patients with IMN with urinary protein excretion greater than 3.5 g/24 hours for at least six months received four weekly infusions of the anti-CD20 antibody rituximab (375 mg/m2). Proteinuria decreased from 8.6 ± 4.2 g/24 hours at baseline to 4.3 ± 3.3 at three months (-51%; P < .005) and to 3.0 ± 2.5 at 12 months (-66%; P < .005). At 12 months, proteinuria decreased to not more than 0.5 g/24 hours in two patients and to not more than 3.5 g/24 hours in three patients. In the remaining three patients, proteinuria decreased by 74%, 44%, and 41%. Albumin fractional clearance decreased from 2.3 ± 2.1 at baseline to 1.2 ± 1.7 at three months (-47%; P < .05) and to 0.5 ± 0.6 at 12 months (-76%; P < .003). Serum albumin concentration increased from 2.7 ± 0.5 mg/dL at baseline to 3.1 ± 0.3 mg/dL at three months (+21%; P < .05) and to 3.5 ± 0.4 mg/dL at 12 months (+41%; P < .05). In all patients, progressive decrease in body weight, diastolic blood pressure, and serum cholesterol paralleled improvement in edema. Renal function stabilized (Delta1/creatinine: +0.002 ± 0.007) and CD20 B lymphocytes fell below normal ranges up to the end of the study. Treatment was well-tolerated, with no reports of major drug-related events or changes in other laboratory parameters. "Rituximab thus promotes sustained disease remission in patients otherwise predicted to progress to ESRD, and it is safe," the authors write. "The long-term risk/benefit profile of this novel, disease-specific approach seems much more favorable to that of commonly employed immunosuppressive drugs." The authors suggest that the effect of rituximab was probably mediated by specific drug-related effects on autoreactive B cell clones, thus offering a new and more targeted approach to treatment of IMN than that of nonspecific immunosuppression and to the conservative approach of ACE inhibition, blood pressure control, and lipid control. "Further studies will clarify whether combination with other immunosuppressive drugs may serve to magnify the antiproteinuric effect of rituximab treatment," they write. "Large, randomized trials with longer follow-up are also needed to verify the long-term tolerability of rituximab therapy and its specific renoprotective potential vis-à-vis more conventional immunosuppressive regimens and, ideally, conservative treatment alone." J Am Soc Nephrol. 2003;14:1851-1857 Reviewed by Gary D. Vogin, MD medscape.com