Transplantation
Therapeutic Drug Monitoring Optimizes Efficacy of Immunosuppressive Therapy in Organ Transplants
By Roche
May 25, 2005, 20:59

Monitoring the level of CellCept(R)(mycophenolate mofetil) in a patient's blood in the months following an organ
transplant may enable physicians to identify the precise amount of drug needed by each patient to prevent organ rejection without increasing toxicity, thereby optimizing efficacy and tolerability of the drug over time.

According to an analysis of six-month data presented this week at the American Transplant Congress (ATC), using therapeutic drug monitoring (TDM) to personalize CellCept therapy appears to be feasible and well-tolerated in kidney transplant patients, enabling physicians to control the level of active immunosuppression in a patient's system.

TDM for CellCept is gaining interest from the transplant community, as physicians increasingly turn to next-generation treatment regimens that minimize the use of kidney toxic drugs -- such as calcineurin inhibitors (CNI)
-- and increasingly rely on therapies like CellCept.

"Our six-month data show that TDM with CellCept is feasible and is a well-tolerated approach to treatment in kidney transplant patients," said Professeur Yann Le Meur, Service de Nephrologie, Centre Hospitalier Universitaire Dupuytren in France.

CellCept is the leading immunosuppressant approved for the prevention of organ rejection in patients receiving kidney, heart and liver transplants in combination with cyclosporine and corticosteroids. It has been used in
clinical practice for ten years with more than four million prescriptions filled in the United States. CellCept works to suppress the immune system and prevent organ rejection. The FDA approved dosage for CellCept for adultkidney transplant recipients is 2 g daily.

"To optimize use of CellCept in next-generation immunosuppressive regimens, we have initiated the large-scale OptiCept(TM) study to evaluate TDM strategies. The goal is to minimize toxicity and maximize efficacy of
CellCept-containing regimens," said Robert Gordon, M.D., senior medical director at Roche and a former transplant surgeon. "We hope to provide the transplant community with robust information on monitoring CellCept levels so that physicians can assess when to implement TDM strategies in their kidney transplant patients."

Study Details:

Personalized Dosing vs Fixed Dose of CellCept in Kidney
Transplantation

Prof. Le Meur and his colleagues reported results of a multicenter open-label study of 137 kidney transplant recipients randomized to receive cyclosporine, basiliximab and steroids with either standard-dose CellCept (2 g/day) or a personalized dose (TDM) of CellCept. At six months,
investigators reported that TDM with CellCept is feasible and well-tolerated in kidney transplant patients. Incidence of biopsy-proven acute rejection and patient and organ survival was similar in both dosing groups. In addition,
the personalized dose (TDM) group showed no increase in bacterial infections, CMV infections, gastrointestinal adverse event, leucopenia or anemia.

Patients in the personalized dose (TDM) group received a CellCept dose based on measurement of CellCept blood concentrations at several time points.

Overall, an increased daily dose of CellCept was required to reach the predefined target level of drug in the blood. However, this did not lead to an increase in adverse effects.

Large-Scale OptiCept(TM) Study Underway

To expand upon these preliminary findings, Roche has initiated the OptiCept(TM) study, a large clinical trial to evaluate the feasibility and value of therapeutic drug monitoring for CellCept in kidney transplant patients. More than 700 kidney transplant recipients will be enrolled across 60 transplant centers in the United States. The OptiCept(TM) study will compare traditional fixed dosing of CellCept with personalized dose adjustment based on measurement of CellCept blood concentrations. Study participants will receive CellCept in combination with other drugs, including full-dose or reduced-dose calcineurin inhibitors.

CellCept -- A Cornerstone of Treatment for 10 Years

CellCept is an immunosuppressant or anti-rejection drug approved for use in combination with other immunosuppressive drugs (cyclosporine and corticosteroids) for the prevention of rejection in patients receiving kidney, heart and liver transplants. Ten years after its initial approval by the FDA, CellCept is the most frequently used branded immunosuppressant in the United
States, with more than four million prescriptions written. CellCept received FDA approval for the prevention of organ rejection in kidney transplantation in May 1995, heart in February 1998, and liver in July 2000. The FDA approved
dosages for CellCept are: for adult kidney transplants, 2 g daily; for pediatric kidney transplants, oral suspension 600 mg/m2; for adult heart and liver, 3 g/day.

Additional CellCept Information

There are no adequate and well-controlled studies in pregnant women. As CellCept (mycophenolate mofetil) has been shown to have teratogenic effects in animals at subclinical doses on a body surface area basis, it may cause fetal harm when administered to a pregnant woman. CellCept should not be used in pregnant women unless the potential benefit justifies the potential risk to the fetus. Women of childbearing potential should have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within one week prior to beginning therapy even where there has been a history of infertility,
unless due to hysterectomy.

Women of childbearing potential must use effective contraception before beginning CellCept therapy, during therapy and for six weeks following discontinuation of therapy. Two reliable forms of contraception must be used
simultaneously unless abstinence is the chosen method. If pregnancy occurs during treatment, the physician and patient should discuss the desirability of continuing the pregnancy (see complete product information).

Adverse events reported in more than 30% of renal, cardiac or liver transplant patients receiving CellCept (in combination with cyclosporine and corticosteroids) were pain, fever, headache, asthenia, anemia, leukopenia(1),
thrombocytopenia, leukocytosis, urinary tract infection, hypertension, hypotension, peripheral edema, hypercholesteremia, hypokalemia, hyperglycemia, creatinine, BUN and cough increased, hypomagnesemia, diarrhea, constipation, nausea, vomiting, respiratory infection, dyspnea, lung disorder, pleural effusion, tremor and insomnia.

Patients receiving immunosuppressant regimens are at increased risk of developing lymphomas and other malignancies, particularly of the skin.

Warning:

Increased susceptibility to infection and the possible
development of lymphoma may result from immunosuppression. Only physicians experienced in immunosuppressive therapy and management of renal, cardiac or hepatic transplant patients should use CellCept. Patients receiving the drug
should be managed in facilities equipped and staffed with adequate laboratory and supportive medical resources. The physician responsible for maintenance therapy should have complete information requisite for the follow-up of the
patient.

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