Induction Therapy of CMV Retinitis: In one randomized open-label controlled study, 160 patients with AIDS and newly diagnosed CMV retinitis were randomized to receive treatment with either VALCYTE tablets (900 mg twice daily for 21 days, then 900 mg once daily for 7 days) or with intravenous ganciclovir solution (5 mg per kg twice daily for 21 days, then 5 mg per kg once daily for 7 days). Study participants were: male (91%), White (53%), Hispanic (31%), and Black (11%). The median age was 39 years, the median baseline HIV-1 RNA was 4.9 log10, and the median CD4 cell count was 23 cells/mm3. A determination of CMV retinitis progression by the masked review of retinal photographs taken at baseline and Week 4 was the primary outcome measurement of the 3-week induction therapy. Table 19 provides the outcomes at 4 weeks.

Maintenance Therapy of CMV Retinitis: No comparative clinical data are available on the efficacy of VALCYTE tablets for the maintenance therapy of CMV retinitis because all patients in the CMV retinitis study received open-label VALCYTE tablets after Week 4. However, the AUC for ganciclovir is similar following administration of 900 mg VALCYTE tablets once daily and 5 mg per kg intravenous ganciclovir once daily. Although the ganciclovir Cmax is lower following VALCYTE tablets administration compared to intravenous ganciclovir, it is higher than the Cmax obtained following oral ganciclovir administration. Therefore, use of VALCYTE tablets as maintenance therapy is supported by a plasma concentration-time profile similar to that of two approved products for maintenance therapy of CMV retinitis. 

Prevention of CMV Disease in Heart, Kidney, Kidney-Pancreas, or Liver Transplantation: A double blind, double-dummy active comparator study was conducted in 372 heart, liver, kidney, or kidney-pancreas transplant patients at high risk for CMV disease (D+/R-). Patients were randomized (2 VALCYTE: 1 oral ganciclovir) to receive either VALCYTE tablets (900 mg once daily) or oral ganciclovir (1000 mg three times a day) starting within 10 days of transplantation until Day 100 post-transplant. The proportion of patients who developed CMV disease, including CMV syndrome and/or tissue-invasive disease during the first 6 months post-transplant was similar between the VALCYTE tablets arm (12.1%, N=239) and the oral ganciclovir arm (15.2%, N=125). However, in liver transplant patients, the incidence of tissue-invasive CMV disease was significantly higher in the VALCYTE group compared with the ganciclovir group. These results are summarized in Table 20.

Mortality at six months was 3.7% (9/244) in the VALCYTE group and 1.6% (2/126) in the oral ganciclovir group.

Prevention of CMV Disease in Kidney Transplantation: A double-blind, placebo-controlled study was conducted in 326 kidney transplant patients at high risk for CMV disease (D+/R-) to assess the efficacy and safety of extending VALCYTE CMV prophylaxis from 100 to 200 days post-transplant. Patients were randomized (1:1) to receive VALCYTE tablets (900 mg once daily) within 10 days of transplantation either until Day 200 post-transplant or until Day 100 post-transplant followed by 100 days of placebo. Extending CMV prophylaxis with VALCYTE until Day 200 post-transplant demonstrated superiority in preventing CMV disease within the first 12 months post-transplant in high risk kidney transplant patients compared to the 100 day dosing regimen (primary endpoint). These results are summarized in Table 21.

The percentage of kidney transplant patients with CMV disease at 24 months post-transplant was 38.7% (63/163) for the 100 day dosing regimen and 21.3% (33/155) for the 200 day dosing regimen.