Aspreva Pharmaceuticals Corporation (VICTORIA, BC, Canada) an emerging pharmaceutical company focused on identifying, developing, and commercializing new indications for approved drugs and late-stage drug candidates for patients living with less common diseases, announced the completion of the targeted enrollment of 358 patients in its global 117-site phase III clinical trial for CellCeptR (mycophenolate mofetil, F. Hoffmann-La Roche) in the treatment of lupus nephritis. The study is assessing the safety and efficacy of CellCept in inducing response and maintaining remission in patients with biopsy-proven lupus nephritis.

The two-phase induction and maintenance study is a randomized open-label comparison of mycophenolate mofetil with the current standard of care, intravenous cyclophosphamide, for the first 6 months (induction phase), followed by a double-blind comparison of mycophenolate mofetil with azathioprine for up to 3 years (maintenance phase). The primary end point for the induction phase is an improvement in proteinuria and stabilization of serum creatinine. The company expects database lock on the induction phase of the study in the second quarter of 2007 with submission of an sNDA to the US FDA in the fourth quarter of 2007.

Lupus nephritis is the most serious manifestation of systemic lupus erythematosus (SLE), which, if left untreated, can lead to kidney failure, requiring dialysis. It is a complicated disease as patients typically fluctuate between periods of intense disease activity when the patient's own immune system is actively attacking and causing damage in their kidney, interspersed with periods of remission. Clinicians estimate that one third to one half of lupus patients have lupus nephritis. There has been no new approved treatment for SLE or lupus nephritis in the US in over 30 years. Current treatments involve the off-label use of existing cancer drugs such as cyclophosphamide, steroids and other immunosuppressant drugs such as azathioprine.

CellCept is Roche's leading immunosuppressant or "anti-rejection" drug used in combination with other immunosuppressive drugs (cyclosporine and corticosteroids) for the prevention of rejection in patients receiving heart, kidney, and liver transplants. Over the last decade, CellCept has become the world's most widely studied immunosuppressant and research is ongoing both in organ transplantation and related areas, such as autoimmune disease, to help provide clinical benefit to a wider range of patients.

In July 2003, Aspreva signed a collaboration agreement with Roche for the exclusive worldwide rights (excluding Japan) to develop and, upon regulatory approval, commercialize CellCept for all autoimmune disease applications. In 2006, Aspreva and Roche received orphan srug designation from the FDA for CellCept in pemphigus vulgaris and completed patient enrollment in a pemphigus vulgaris phase III clinical trial. This trial is a randomized, double-blind, placebo- controlled comparison study of CellCept and placebo to investigate the efficacy and safety of CellCept for patients with pemphigus vulgaris over a treatment period of 52 weeks. The primary endpoint encompasses both minimal disease activity, defined as no new persistent lesions, together with a low steroid dose. The trial is anticipated to be completed in 2007.

—A. Techman

The Rheumatologic Perspective

Mycophenylate is already widely used to treat lupus nephritis based on the results of small trials or larger unblinded trial data. Part of the reason for its acceptance relates to the slow development of effective new agents to treat patients with lupus and the high frequency of adverse events and poor patient acceptance of the "gold" standard, cyclophosphamide. To make the matter more complex, the "gold" standard has never been approved for treatment of lupus. This makes clinical trials more difficult because the comparison is between the new agent (in this case mycophenylate) and the unapproved but clinically accepted standard. One can only hope that the now fully enrolled trial was sufficiently powered to yield interpretable data that may be useful in the evaluation of current approaches to treatment of patients with SLE.


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