SOUTH SAN FRANCISCO, Calif.—The U.S. Food and Drug Administration has approved increasing the length of therapy with Valcyte (valganciclovir hydrochloride) in adult kidney transplant patients at high risk for cytomegalovirus (CMV) disease, according to an Aug. 10 news release from Genentech.
The supplemental approval is based on data that showed longer prophylactic treatment with Valcyte reduced the incidence of CMV disease in high-risk adult kidney transplant patients from 36.8 percent (for patients who received 100 days of treatment) to 16.8 percent (for patients who received treatment for 200 days) at one year after receiving a transplanted kidney (p<0.0001), according to Genentech.
The overall safety profile of Valcyte did not change with the extension of prophylaxis in high-risk kidney transplant patients.
"Among the different risks people face after a kidney transplant, CMV is one that may be prevented through prophylactic treatment with Valcyte," said investigator, Dr. Atul Humar, Director, Transplant Infectious Diseases and Associate Professor, Department of Medicine, University of Alberta, Canada. "Data now demonstrate that we may further reduce the risk of CMV infection by increasing the duration of preventative treatment from 100 to 200 days."
CMV is a major cause of illness and disease during the first six months following transplantation. It is estimated that 50-80 percent of all adults are infected with the CMV virus, which most often lies dormant in the body throughout life. The virus can be activated at times when the immune system is weakened such as after organ transplantation. CMV infection may cause complications in the lungs, kidneys, nervous system, liver, and gastrointestinal tract.
"Despite advances in the management of CMV, studies have shown that more than a third of patients still develop CMV infection even after 100 days of prophylaxis," said Hal Barron, MD, Genentech’s executive vice president, Global Development and chief medical officer. "This approval provides important information for physicians treating high-risk adult patients during the critical period after kidney transplant."
The IMPACT study for the prevention of CMV disease in adult kidney allograft (transplant) recipients was a global, multi-center (65 centers in 13 countries including the United States), double-blind study that randomized 326 high-risk (donor CMV seropositive/recipient CMV seronegative) kidney allograft recipients to one of two treatment groups: 100 days Valcyte (900 mg once daily) post-transplant followed by 100 days placebo, and 200 days Valcyte (900 mg once daily) post-transplant
The primary endpoint of the study was the proportion of patients who developed protocol-defined CMV disease within the first 52 weeks (12 months) post-transplant. Secondary endpoints included safety, time to CMV disease, time to CMV infection, acute rejection, and graft loss. Definitions of CMV disease were consistent with the American Society of Transplantation (AST) guidelines for use in clinical trials.
The most common adverse events occurring in the Valcyte-treated patients (200 day and 100 day groups) were low white blood cell counts (26 percent vs. 38 percent), diarrhea (26 percent vs. 31 percent), and swelling in the extremities (peripheral edema) (21 percent vs. 19 percent).(3) The most serious adverse events in the Valcyte-treated patients were hypertension (12 percent vs. 13 percent), transplant rejection (6 percent vs. 9 percent), and tremors (17 percent vs. 12 percent). Four deaths, unrelated to treatment with Valcyte, occurred in the 100-day treatment group. These were attributed to hemorrhage (one), sepsis (one) or septic shock (two).
The percentage of kidney transplant patients with CMV disease at 24 months post-transplant was 38.7 percent (63/163) for the 100 day dosing regimen and 21.3 percent (33/155) for the 200 day dosing regimen (p=0.0008).
