Cellcept

Researchers seeking to enhance transplant patient care with less toxic drug regimens presented early findings of a steroid-free treatment regimen in liver transplant recipients with hepatitis C. One-year data from an open label study reported Sunday at the American Transplant Congress (ATC) suggests that a steroid-free treatment regimen including CellCept® (mycophenolate mofetil) provided comparable efficacy and safety to a standard steroid-containing protocol. CellCept is approved for the prevention of organ rejection in combination with cyclosporine and corticosteroids in patients receiving kidney, heart and liver transplants.

Steroids have been a cornerstone of transplant therapy for the past 50 years. However, long-term steroid use has shown significant side effects, which can include bone and muscle problems, eye disease, delayed wound healing and decreased ability to fight infection. For patients with hepatitis C, steroids are widely recognized to have an adverse effect on virus replication, putting them at an increased risk for hepatitis C recurrence following liver transplantation.

"The question has always been: how do we achieve the right balance of immunosuppression to prevent acute rejection without over-suppressing the immune system, which would allow hepatitis C virus to rapidly replicate?" said Goran Klintmalm, M.D., principal investigator, who is Chief and Chairman of the Baylor Regional Transplant Institute, Baylor University Medical Center, Dallas. "In our study, the steroid-free CellCept regimen demonstrated comparable efficacy, without increasing the risk of hepatitis C recurrence. We are encouraged by these trends at one year."

Study Background and Results(1)

A total of 312 adult hepatitis C liver transplant patients participated in the open-label, prospective multicenter study. Patients were randomized to one of three treatment regimens: tacrolimus and prednisone (arm one); CellCept, tacrolimus and prednisone (arm two); or CellCept, tacrolimus, and three-dose Zenapax® (daclizumab) without steroids (arm three). Primary endpoints in the study were clinically significant differences in acute cellular rejection (ACR) and/or clinically significant differences in hepatitis C recurrence. Acute rejection rates were 16%, 9% and 5% in the three arms, respectively.

A total of 151 patients had one-year follow-up data available for the preliminary analysis presented at ATC. Study results found that hepatitis C recurrence was comparable across all arms. Additionally, the CellCept-based steroid-free regimen was comparable to the standard steroid-containing regimens in organ survival, patient survival and incidence of adverse events (infections, malignancies, hyperlipidemia and diabetes).

Additional Study Underway

"With transplant physicians around the world using CellCept for more than a decade to prevent organ rejection in their transplant patients, Roche is looking to the future," said Robert Gordon, M.D., senior medical director at Roche and a former transplant surgeon. "We're evaluating new, low-toxicity regimens with CellCept that we hope will further improve patient outcomes."

Roche recently initiated the Liver Spare the Nephron (STN) study, a prospective, open-label randomized trial to evaluate low toxicity regimens including CellCept. The study will take place in more than 35 transplant centers in the U.S. and Canada. The study, which will recruit 340 liver transplant recipients, is designed to evaluate the efficacy and safety of a regimen of CellCept with either sirolimus or standard calcineurin inhibitors (CNI). Investigators will evaluate the effect of these regimens on preservation of renal function and prevention of acute rejection, organ loss and patient survival.

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 approval by the FDA, CellCept is the most frequently used branded immunosuppressant in the United States with more than four million prescriptions filled. CellCept received FDA approval for the prevention of organ rejection in transplanted kidneys in 1995, in hearts in 1998 and in livers in 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 > 30% of renal, cardiac or liver transplant patients receiving CellCept (in combination with cyclosporine and corticosteroids) were pain, fever, headache, asthenia, anemia, leukopenia(2), 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. For full prescribing information, visit www.rocheusa.com/products/cellcept/pi.html.

About Roche - More Than a Century in the U.S. and the World

Founded in 1896 and headquartered in Basel, Switzerland, Roche is one of the world's leading innovation-driven healthcare groups. Its core businesses are pharmaceuticals and diagnostics. Roche is one of the world's leaders in diagnostics, the leading supplier of pharmaceuticals for cancer, as well as a leader in virology and transplantation. As a supplier of products and services for the prevention, diagnosis and treatment of disease, the Group contributes on many fronts to improve people's health and quality of life. Roche employs roughly 65,000 people in 150 countries, including approximately 15,000 in the United States.

Roche's U.S. operations celebrate their American Centennial in 2005. In another milestone this year, Roche was named in January to Fortune magazine's list of Best Companies to Work for in America. One of an increasingly rare breed of major healthcare companies that still bear their original name, Roche today has more than a dozen U.S. sites located in California, Colorado, Indiana, New Jersey and South Carolina, as well as in Puerto Rico. Roche has alliances and research and development agreements with numerous partners, including majority ownership interests in Genentech and Chugai. Roche's Pharmaceuticals Division offers a portfolio of leading medicines in therapeutic areas including cancer, HIV/AIDS, hepatitis C, transplantation, dermatology and influenza. Roche's Diagnostics Division supplies a wide array of innovative testing products and services to researchers, physicians, patients, hospitals and laboratories worldwide. For further information, please visit our worldwide and U.S. websites (Global: www.roche.com and U.S.: www.roche.us).

(1) Fasola CG, Klintmalm GB, et al. Abstract #475: “Multicenter Randomized Hepatitis C (HCV) Three Trial Post-Liver Transplantation (OLT): A One-Year Follow-Up Report.”

(2) Patients should be monitored for neutropenia. Dosing should be interrupted or the dose reduced if neutropenia develops.

Contacts: Maureen Byrne Roche Office: (973) 562-2203 Cell: (973) 800-5097 Freya Leff Ketchum Office: (646) 935-4050 Cell: (646) 338-9567