Regulatory Decision Summary for Eraxis

The purpose of this Supplemental New Drug Submission (SNDS) was to expand the indication for Eraxis in the treatment of candidiasis/candidemia to pediatric patients at least 1 month of age. Upon review, an indication in the treatment of candidiasis/candidemia in non-neutropenic pediatric patients at least 1 month of age was authorized.

The proposed expansion of the indication for Eraxis to pediatric patients was supported by a prospective, open-label, non-comparative, multi-national study A8851008 that assessed the safety and efficacy of anidulafungin in 68 pediatric patients aged 1 month to <18 years with invasive candidiasis/candidaemia (ICC). Safety was the primary endpoint in the study, and all efficacy evaluations were secondary endpoints. Patients were stratified by age (1 month to <2 years, 2 to <5 years, and 5 to <18 years) and received once-daily intravenous anidulafungin (3.0 mg/kg loading dose on Day 1, and 1.5 mg/kg daily maintenance dose thereafter) for up to 35 days followed by an optional switch to oral fluconazole (6-12 mg/kg/day, maximum 800 mg/day). Patients were followed at 2 and 6 weeks after end-of-treatment (EOT).

The adverse event profile of the 68 pediatric subjects in study A8851008 was similar to that observed in adults with ICC. However, the frequencies of certain hepatobiliary adverse events, including alanine aminotransferase (ALT) increased and aspartate aminotransferase (AST) increased were reported at a higher frequency (7-10%) in these pediatric patients compared to adults (2%). Although chance or differences in underlying disease severity may have contributed, it cannot be excluded that hepatobiliary adverse reactions occur more frequently in pediatric patients compared to adults. This information is presented in the Eraxis Product Monograph.

Among 68 patients who received Eraxis in study A8851008, 64 had microbiologically confirmed Candida infection and were evaluated for efficacy (i.e., a successful global response) in the modified intent-to-treat (MITT) population. Overall, 61 patients (92.2%) had Candida isolated from blood only. The most commonly isolated pathogens were Candida albicans (25 [39.1%] patients), Candida parapsilosis (17 [26.6%] patients), and Candida tropicalis (9 [14.1%] patients). A successful global response was defined as having both a clinical response of success (cure or improvement) and a microbiological response of success (eradication or presumed eradication). At the end of intravenous treatment (EOIVT), the overall rate of successful global response was 70.3% (95% CI: 57.6, 81.1). At EOT, the rates of successful global response were 71.9% (95% CI: 59.2, 82.4) at the 2-week follow-up and 67.2% (95% CI: 54.3, 78.4) at the 6-week follow-up.

Study A8851008 did not include sufficient number of neutropenic pediatric patients to make any conclusions regarding the efficacy of Eraxis in this patient population; therefore, an authorized indication for Eraxis is restricted to non-neutropenic pediatric patients at least 1 month of age.

In the population pharmacokinetic analysis of combined data from adult and pediatric patients with ICC, the mean exposure parameters (AUC_0-24 and C_min) of Eraxis at steady state in pediatric patients were comparable to those in adults receiving 200 mg loading dose and 100 mg/day maintenance dose.

Based on the review of submitted evidence, Health Canada considers that the benefit-harm-uncertainty profile of Eraxis is favourable for the treatment of invasive candidiasis/candidemia in non-neutropenic pediatric patients at least 1 month of age under the conditions of use included in the Eraxis Product Monograph at this time. The efficacy and safety of Eraxis have not been established in neonates (less than 1 month of age) and therefore, Health Canada has not authorized an indication in this patient population.

For further details about Eraxis, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.