From the Archives: Fall 2005 Issue of Lupus Now Magazine
Drug Spotlight: Mycophenolate Mofetil for Lupus Kidney Disease
Mycophenolate mofetil (MMF) (CellCept) has been approved by the Food and Drug Administration (FDA) to prevent rejection after organ transplants. However, some physicians have now begun to use this Roche Pharmaceuticals product "off-label" (that is, a use not approved by the FDA) in an attempt to control the activity of various autoimmune diseases.
Several small studies and anecdotal reports have suggested that MMF may be an effective and well-tolerated alternative in treating lupus kidney disease (lupus nephritis) compared to the standard-of-care treatments, such as intravenous (IV) cyclophosphamide and azathioprine. Preliminary results from one study, a recently completed trial, showed the following important results: In the initial treatment (or induction) study, MMF was at least as efficacious as IV cyclophosphamide at bringing about remission of active lupus nephritis. That is, there was the same amount of improvement in renal abnormalities (such as proteinuria, serum creatinine, and urine microscopic findings) among the participants. However, MMF was superior to IV cyclophosphamide in bringing about complete responses in some patients with lupus nephritis (i.e., normalization of kidney function).
Small studies have also been conducted comparing MMF to a combination of IV cyclophosphamide and azathioprine in maintenance therapy of lupus nephritis, and in a long-term study of up to five years, assessing remission of lupus nephritis. Both studies show MMF to be at least as efficacious as cyclophosphamide, but with a more favorable tolerability profile.
Despite these findings, it is important to note that MMF is not approved, nor has it been fully proven yet as safe or effective for any autoimmune disease treatment purposes, by any regulatory body. More studies are needed in order to determine whether these early promising findings are accurate.
A study of MMF is currently being conducted by Aspreva Pharmaceuticals, in a partnership agreement with Roche Pharmaceuticals. The purpose of this study is twofold: to provide further information on whether MMF has an effect in the initial treatment of lupus nephritis (induction phase) and to assess how well it maintains any such effect over longer periods when compared to current standard treatments (maintenance phase).
Unlike the other studies published so far, this trial will include a large number of participants (the goal is to recruit 358 patients), which will make it the largest study of MMF in lupus nephritis to date. The induction phase of this two-phase international trial includes a six-month open-label test of MMF versus the current standard of care, IV cyclophosphamide. The primary endpoint for the induction phase can be summarized as an improvement in the amount of protein that is spilled from the kidney, normalization of a blood test called serum creatinine, and absence of blood in the urine.
Following completion of the induction phase of the trial, patients will be re-randomized into a comparison of MMF against azathioprine during the maintenance phase for up to three years, to assess the drug's long-term safety and efficacy. This second study will be double-blind, meaning that neither the patient nor the study doctors will know which of these two treatments the patient is taking. The primary endpoint for the maintenance phase is treatment failure, defined as one of the following: death, end-stage kidney disease (meaning that the patient is on dialysis or has had a kidney transplant), doubling of serum creatinine in a blood test, flare of active lupus in the kidneys, or significant flare of lupus outside of the kidney.
This study is being conducted at clinical sites in Alabama, California, Florida, Georgia, Illinois, Massachusetts, Missouri, New York, North Carolina, Ohio, Oklahoma, Pennsylvania, South Carolina, and Texas. To find a participating clinic near you, log on to clinicaltrials.gov and search "ALMS," or call Karen O'Brien at PPD Clinical Research at 512-685-5662.