Brincidofovir (CMX001) Is Well Tolerated in Highly Immunocompromised Pediatric Patients

Background: Brincidofovir (BCV, CMX001) is a Phase 3 broad-spectrum antiviral in development for the prevention of dsDNA viral infections in immunocompromised patients. Since pediatric patients pose unique toxicity challenges and dsDNA viral infections are common in this age group, we undertook an analysis of the collective safety experience in pediatric subjects receiving BCV.

Methods: All pediatric subjects (<18 years) received oral BCV weekly or twice-weekly under EINDs, in the open-label expanded access Study 350, and in placebo-controlled Study 202 for the preemptive treatment of adenovirus (AdV) infection. In Study 202, BCV was administered with food and guidance on the management of gastrointestinal (GI) disturbances was provided to the investigators.

Results: 147 pediatric subjects (median 7 years, range 3 months to 17 years) received a median of 7 weeks of BCV (range 1 to 44), with 45 subjects receiving at least 10 weeks of 4 mg/kg/week. Subjects were predominantly hematopoietic cell transplant (HCT) recipients. Consistent with data from adult immunocompromised subjects, the most frequently reported adverse events (AEs) were GI disturbances, with diarrhea of any grade reported in 48% of subjects in Study 202 and 43% in Study 350 and EINDs. Grade 3/4 diarrhea was reported in 13% (Study 202) and 12% (Study 350) of subjects. Less than 10% of subjects across Studies 202 and 350 discontinued BCV for GI symptoms. Transient increases in ALT were reported in 4% (Study 202) and 12% (Study 350 and EINDs) of subjects, predominantly <5x ULN (grade 2) and not requiring discontinuation of BCV. In Study 202, the incidence of GI and ALT events leading to study drug discontinuation was not higher in the BCV group than in the placebo group, although the interpretation of these data is limited by the small sample size. Based on treatment emergent laboratory abnormalities, no indications of renal toxicity or hematologic toxicity including neutropenia were observed, including subjects who received higher BCV dose or longer durations of treatment.

Conclusions: A review of data from pediatric subjects treated with brincidofovir did not indicate any previously unidentified safety signals. In these subjects, as in adults, there was no indication of hematologic or renal toxicity. The safety and tolerability profile in adults and pediatric patients to date support the continued development of brincidofovir as prevention for dsDNA viral diseases.