Drug can fight adenovirus in HSCT recipients
Image by Yale Rosen
NEW ORLEANS—Interim results of a phase 3 trial suggest brincidofovir can treat adenovirus (AdV) infection in recipients of allogeneic hematopoietic stem cell transplant (HSCT).
Both pediatric and adult patients experienced a decline in AdV viral load after brincidofovir treatment, but pediatric patients were more likely to respond.
Overall survival rates were better for patients who had a rapid response and were therefore better among pediatric patients than adults.
Investigators said the adverse events (AEs) in this study were consistent with the known safety profile of brincidofovir.
Michael Grimley, MD, of Cincinnati Children’s Hospital in Ohio, and his colleagues presented these results at IDWeek 2016 (abstract 2339). The research was supported by Chimerix, the company developing brincidofovir.
This trial, known as AdVise, was designed to evaluate brincidofovir for the treatment of AdV infection in pediatric and adult patients divided into 3 cohorts:
- Cohort A consists of allogeneic HSCT recipients with asymptomatic or limited AdV infection
- Cohort B consists of allogeneic HSCT recipients with disseminated AdV disease
- Cohort C consists of autologous HSCT recipients, solid organ transplant recipients, and other immunocompromised patients.
All patients were assigned to 12 weeks of oral brincidofovir, administered twice weekly. An additional 12 weeks of treatment was allowed in patients with ongoing or recurrent infection. After completing treatment, all patients were followed until week 36.
Interim analysis
The investigators examined outcomes at 24 weeks after the first brincidofovir dose (12 weeks after prescribed dosing duration) in 158 patients, including:
- Cohort A—23 adults and 43 pediatric patients
- Cohort B—35 adults and 57 pediatric patients.
The investigators noted that many of the patients did not complete the study. The team said this is a reflection of the significant mortality risk of AdV because most of these patients died before they could finish.
Sixty-five percent of adults and 33% of children in Cohort A did not complete the study. The same was true for 71% of adults and 49% of children in Cohort B.
Mortality
The study’s primary efficacy endpoint is all-cause mortality at day 60 after the first brincidofovir dose in allogeneic HSCT recipients with disseminated AdV disease (Cohort B). All-cause mortality at day 60 in this cohort was 19% in pediatric patients and 43% in adults.
In Cohorts A and B, all-cause mortality at 24 weeks was lower in children than adults.
At 24 weeks, pediatric all-cause mortality was 33% in Cohort A and 42% in Cohort B. Adult all-cause mortality was 48% in Cohort A and 71% in Cohort B.
AdV-related mortality at 24 weeks in pediatric patients was 9% in Cohort A and 14% in Cohort B. AdV-related mortality in adults was 4% in Cohort A and 46% in Cohort B.
Declines in viremia
In Cohort A, 61% of patients achieved undetectable viremia at the end of treatment—43% of adults and 70% of children.
In Cohort B, 49% of patients achieved undetectable viremia at the end of treatment—29% of adults and 63% of children.
The median time to undetectable AdV viremia was 43 days (range, 8 to non-estimable) for adults in Cohort A, 14 days (range, 5 to 23) for children in Cohort A, non-estimable (range, 29 days to non-estimable) for adults in Cohort B, and 22 days (range, 15 to 36) for children in Cohort B.
Link between response and survival
The investigators conducted post-hoc analyses to assess the correlation between rapid virologic response to brincidofovir and time to subsequent mortality.
The team compared patients who responded to treatment—defined as achieving a ≥ 2-log10 copies/mL decline, undetectable AdV viremia at week 4, or undetectable AdV viremia at week 6—with non-responders.
