CellCept® (mycophenolate mofetil capsules)

Two CellCept Trials In MG Disappointing. Two large trials of the potent immunosuppressant myocophenolate mofetil (CellCept) in the autoimmune disease myasthenia gravis (MG) have, surprisingly, yielded results that suggest the drug is no better than standard treatment with the corticosteroid prednisone in this disease. In MG, the immune system mounts a damaging attack against the place on muscle fibers that normally receives signals from nerve fibers. The findings from both studies were published in the Aug. 5 issue of Neurology. Both trials were double-blind, meaning neither participants nor investigators knew which substance was being taken; and randomized, meaning each participant had an equal chance of being assigned to receive the study drug or a placebo (inactive substance). The first, a 13-center, U.S.-based study of 80 people with MG, compared 2.5 grams per day of mycophenolate mofetil plus 20 milligrams a day of prednisone, to a placebo plus 20 milligrams a day of prednisone, over three months. The investigators, coordinated by Donald Sanders at Duke University, were members of the Muscle Study Group, which includes several MDA clinic directors. They measured changes in muscle strength and function between the start and end of the study, using a standardized MG scale. The average change in score on the "quantitative myasthenia gravis" scale was similar in the prednisone-plus mycophenolate and the prednisone-plus-placebo groups. The second study, an international trial that included 88 participants from 43 centers in several countries, included patients with MG who had been taking prednisone for at least four weeks. Donald Sanders coordinated the publication group. Participants were randomly assigned to additional treatment with either 2 grams per day of mycophenolate mofetil or a placebo for nine months, while their prednisone dosage was gradually reduced on a predetermined schedule. They were evaluated on the quantitative MG scale, as well as on scales of activities of daily living and a general health survey. Mycophenolate mofetil wasn't any better than a placebo at maintaining MG control during the nine months of prednisone dose reduction. In the same issue of Neurology, Michael Benatar, co-director of the MDA clinic at Emory University in Atlanta and an MDA research grantee, and Lewis Rowland, former director of the MDA/ALS Center at Columbia University in New York and a former MDA research grantee, probed some of the explanations the investigators offered as an alternative to concluding that mycophenolate mofetil simply isn't any more effective than prednisone in MG. Benatar and Rowland describe mycophenolate's ability to block the proliferation of key cells in the immune system and its success in patients with kidney transplants. They note that encouraging case reports and one small double-blind study, as well as "conversations among neurologists," had popularized the use of the drug in MG. They note that the studies may have been too short to show an effect of mycophenolate; that prednisone may have been more effective than expected in the study participants, leading to an obliteration of any difference between the groups treated with mycophenolate and those treated with prednisone alone; that, in one or both studies, the criteria used to judge change may have been so stringent that small changes patients might consider significant were overlooked; and that the selection criteria may have been too narrow to represent the general MG population. Additional studies will be needed to see whether, over a longer period of time, mycophenolate would offer more benefit with respect to weakness in MG or would allow patients to take less prednisone.

Hoffmann  -          La Roche Inc.

CellCept

Hoffmann-La Roche Inc. (Roche), based in Nutley, N.J.,
is the U.S. prescription drug unit of the Roche Group,
one of the world’s leading research-oriented health
care groups with core businesses in pharmaceuticals
and diagnostics. The company provides innovative
products and services that address prevention,
diagnosis and treatment of diseases, thus enhancing
people's health and quality of life.