Final Results of the CellCept(R) Spare the Nephron (STN) Study Show Maintenance Therapy is Associated with Improved Renal Function

TORONTO, June 1 /PRNewswire/ -- The final results of the Spare the Nephron (STN) study, a multicenter trial investigating a novel kidney-sparing treatment protocol using CellCept(R) (mycophenolate mofetil), showed the CellCept-based regimen in combination with sirolimus (SRL) is associated with improved renal function when compared with the CellCept-based regimen in combination with calcineurin inhibitors (CNI).

Furthermore, the study showed this improvement without increasing the risk of acute rejection, and was tolerated in almost 80 percent of patients. The results were presented today at the American Transplant Congress (ATC) in Toronto.

The STN Trial in kidney transplant recipients examines ways to prevent rejection without damaging kidneys. As transplant patients are living longer, studies suggest that therapies such as CNIs can cause impairment of kidney function, damage to the blood vessels, and filtering capacity of the kidneys. "This study provides strong evidence for the benefits of a CNI-free, CellCept-based regimen," said Thomas Pearson, M.D., lead investigator, Livingston Professor of Surgery, Department of Surgery, Emory University School of Medicine, Atlanta, GA.

The STN trials were conducted at more than 35 transplant centers in the United States and Canada.

"The goal of this study was to optimize the use of immunosuppressants for achieving long-term success," added Dr. Pearson. "The STN Kidney studied the combination of CellCept and SRL with the goal of reducing CNI associated nephrotoxicity therapy to prolong graft and patient survival."

About the Study

This open-label, prospective, multicenter study, randomized 305 patients (maintained on MMF and a CNI) for 30-180 days post-transplant to receive either MMF (1-1.5 g BID) plus SRL (2-10 mg followed by at least 2 mg/day; trough 5-10 ng/mL) and discontinue the CNI (MMF/SRL) or to continue their current regimen (MMF/CNI). Antibody induction and/or corticosteroids were administered according to individual center practices.

Study Results

The 12-month results are from the first 249 patients receiving either the CellCept-based regimen in combination with SRL (n123) or the CellCept-based regimen in combination with CNI (n126).

Investigators found acute rejection in 6.5 percent of the patients (8/123) in the CellCept-based regimen in combination with SRL, compared to 7.1 percent of the patients (9/126) in the CellCept-based regimen in combination with CNI.

Mean time from transplant to randomization in both groups was 117 days. Baseline characteristics and measured GFR values were similar in the treatment groups and 98 patients in the CellCept-based regimen in combination with SRL were receiving tacrolimus. Graft loss was experienced in 1.6 percent of patients (2/123) in the CellCept-based regimen in combination with SRL, compared to 2.4 percent of patients (3/126) in the CellCept-based regimen in combination with CNI.

There were no deaths in the CellCept-based regimen in combination with SRL. Three (3/126) patient deaths were remotely related to the CellCept-based regimen in combination with CNI. The number and proportion of patients withdrawn for adverse events at 12 months was 18.7 percent (23/123) in the CellCept-based regimen in combination with SRL, and 7.1 percent (9/126) in the CellCept-based regimen in combination with CNI.

The percent change from baseline in GFR at 12 months was 25.8 percent for patients in the CellCept-based regimen in combination with SRL, compared to 11.3 percent in the CellCept-based regimen in combination with CNI group. Safety outcomes were similar in both groups.

CellCept is indicated for the prophylaxis of organ rejection in patients receiving allogeneic renal, cardiac or hepatic transplants. CellCept should be used concomitantly with cyclosporine and corticosteroids.

Important Safety Information:

WARNING:

Immunosuppression may lead to increased susceptibility to infection and possible development of lymphoma. 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.

Female users of childbearing potential must use contraception. Physicians should inform female patients that CellCept use during pregnancy is associated with increased rates of pregnancy loss and congenital malformations.

-- Patients receiving immunosuppressive regimens involving combinations of
drugs, including CellCept, as part of an immunosuppressive regimen are
at increased risk of developing lymphomas and other malignancies,
particularly of the skin.
-- Oversuppression of the immune system can also increase susceptibility
to infection, including opportunistic infections, and sepsis.
-- Cases of progressive multifocal leukoencephalopathy (PML), sometimes
fatal, have been reported in patients treated with CellCept.
Hemiparesis, apathy, confusion, cognitive deficiencies and ataxia were
the most frequent clinical features observed. The reported cases
generally had risk factors for PML, including treatment with
immunosuppressant therapies and impairment of immune function. In
immunosuppressed patients, physicians should consider PML in the
differential diagnosis in patients reporting neurological symptoms and
consultation with a neurologist should be considered as clinically
indicated. Consideration should be given to reducing the amount of
immunosuppression in patients who develop PML. In transplant patients,
physicians should also consider the risk that reduced immunosuppression
represents to the graft.
-- CellCept can cause fetal harm when administered to a pregnant woman. A
patient who is planning a pregnancy should not use CellCept unless she
cannot be successfully treated with other immunosuppressant drugs. If
this drug is used during pregnancy, or if the patient becomes pregnant
while taking this drug, the patient should be apprised of the potential
hazard to the fetus.
-- Women of childbearing potential (including pubertal girls and
peri-menopausal women) taking CellCept must receive contraceptive
counseling and use effective contraception. The patient should begin
using her chosen contraceptive method 4 weeks prior to starting
CellCept therapy. She should continue contraceptive use during therapy
and for 6 weeks after stopping CellCept. Two reliable forms of
contraception must be used simultaneously unless abstinence is the
chosen method. Patients should be aware that CellCept reduces blood
levels of the hormones in the oral contraceptive pill and could
theoretically reduce its effectiveness.
-- Severe neutropenia [absolute neutrophil count (ANC) <0.5 x
10cubed/microL] developed in up to 2.0% of renal, up to 2.8% of cardiac,
and up to 3.6% of hepatic transplant patients receiving CellCept 3 g
daily. Patients receiving CellCept should be monitored for neutropenia.
If neutropenia develops (ANC < 1.3 x 10cubed/microL), dosing with
CellCept should be interrupted or the dose reduced, appropriate
diagnostic tests performed, and the patient managed appropriately (see
DOSAGE AND ADMINISTRATION).
-- Gastrointestinal bleeding (requiring hospitalization) has been observed
in approximately 3% of renal, in 1.7% of cardiac, and in 5.4% of
hepatic transplant patients treated with CellCept 3 g daily.
-- Common adverse 20% of patients in CellCept group in controlled events
that were reported in greater than or equal to studies in prevention of
renal, cardiac or hepatic allograft rejection are listed in Table 8 of
the ADVERSE REACTIONS section of the complete Prescribing Information.

About Roche

Hoffmann-La Roche Inc. (Roche), based in Nutley, N.J., is the U.S. pharmaceuticals headquarters of the Roche Group, one of the world's leading research-oriented healthcare groups with core businesses in pharmaceuticals and diagnostics. For more than 100 years in the U.S., Roche has been committed to developing innovative products and services that address prevention, diagnosis and treatment of diseases, thus enhancing people's health and quality of life. An employer of choice, in 2007 Roche was named Top Company of the Year by Med Ad News, one of the Top 20 Employers (Science) and ranked the No. 1 Company to Sell For (Selling Power). In previous years, Roche has been named as a Top Company for Older Workers (AARP) and one of the Best Companies to Work For in America (Fortune). For additional information about the U.S. pharmaceuticals business, visit our website http://www.rocheusa.com/. Product and treatment information for U.S. healthcare professionals is available at www.RocheExchange.com.

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Source: Roche

CONTACT: Christopher Vancheri of Roche, Office, +1-973-562-2203, Cell,
+1-973-262-1175, Christopher.Vancheri@roche.com

Web site: http://www.rocheusa.com/
http://www.rocheexchange.com/

2008-06-01 17:05:01 0374175 PRNEWSWIRE