Oral Cytovene has been approved for the prevention of cytomegalovirus (CMV), a potentially life-threatening infection, in recipients of solid organ transplants.
The FDA approval is based on data, which demonstrate that oral Cytovene given as prophylaxis reduced the overall incidence of CMV disease in liver transplant recipients by 78%.
Oral Cytovene received marketing clearance based on the results of GAN 040, a multinational, randomized, double-blind study compromising 304 orthotopic liver transplant (OLT) recipients randomized (1:1) to receive oral ganciclovir (1000 mg three times daily) or matching placebo, for up to 14 weeks following transplantation.
The six-month incidence of CMV disease was 18.9% in the placebo group compared to 4.8% in the oral Cytovene group. Of the oral Cytovene patients who developed CMV disease, only one (0.7%) developed invasive tissue disease, the most severe type of CMV disease, versus 8.4% percent of placebo patients.
Oral Cytovene helped prevent CMV disease even in those recipients at highest risk for CMV disease--those who were sero-negative for CMV at the time of their transplant and received a CMV sero-positive organ. The six-month incidence of CMV disease in this group was 44% in placebo patients versus 14.8% in oral ganciclovir patients.
Patients who received the most intense immunosuppression also benefited from prophylaxis with oral Cytovene. Of those patients receiving anti-lymphocyte antibodies either for prevention of graft rejection or for treatment of refractory rejection, the incidence of CMV disease was 33% in the placebo group versus 4.6% in the ganciclovir group.
The six-month incidence of herpes simplex was reduced from 23.5% in the placebo arm to 3.5% in those receiving oral ganciclovir prophylaxis.
The most common adverse events in this study were infection, fever, and headache. These events occurred with similar frequency in the ganciclovir-treated and placebo groups.
More than 20,000 people received solid organ transplants (heart, lung, pancreas, kidney, liver, etc.) in the United States in 1995. CMV disease occurs in approximately 15-30% of all solid organ transplant recipients, primarily in the first three months post-transplantation when immunosuppression is most intense--and is a frequent cause of morbidity.
CMV, a member of the herpes family of viruses, infects approximately 50% of the U.S. adult population. In individuals with healthy immune systems, the virus remains in the body in a dormant state. However, among individuals with compromised immune systems, such as organ transplant recipients and people with AIDS, the virus can cause life-threatening and/or sight-threatening illness.
CMV in transplant recipients can cause a debilitating CMV syndrome (fever, malaise), and life-threatening invasive tissue disease (including hepatitis and pneumonia), and increased immunosuppression with resulting secondary infections.