FDA Approves Fidamoxicin for Pediatric C diff

The US Food and Drug Administration (FDA) has approved fidamoxicin (Dificid) for the treatment of children aged 6 months up to 18 years with Clostridiodies difficile (C diff) infections. Additionally, fidamoxicin has also been approved for oral suspension. The approvals were granted to Merck.

“C difficile is an important cause of health care- and community-associated diarrheal illness in children, and sustained cure is difficult to achieve in some patients. The fidaxomicin pediatric trial was the first randomized controlled trial of C difficile infection treatment in children,” Larry K. Kociolek, MD, associate medical director of Infection Prevention and Control at Ann & Robert H. Lurie Children’s Hospital of Chicago, said in the announcement. “I am very excited to have a new C difficile infection treatment option for my pediatric patients.”

Fidamoxicin is a macrolide antibiotic active against gram-positive bacteria.

The FDA’s approval of the new indications was based on a phase 3, multicenter, investigator-blind, randomized, parallel group study (the SUNSHINE study), in which the safety and efficacy of fidaxomicin was evaluated in pediatric patients from 6 months to less than 18 years of age. The study included 148 randomized patients aged <18 years with confirmed C diff infection, of whom 142 received either fidaxomicin (suspension or tablets, twice daily) or vancomycin (suspension or tablets, four times daily) in a 2:1 ratio.

Patients were randomized by age group. "Generally, the two treatment groups were balanced regarding demographics and other baseline characteristics," a Merck press release reports.

C diff associated diarrhea (CDAD) clinical response in the overall pediatric population was assessed through 2 days following 10 days of treatment. It was reported that the clinical response was similar between the fidaxomicin and vancomycin groups (77.6% vs. 70.5%, respectively, with a 95% CI for the treatment difference of 7.5 [-7.4%, 23.9%]). The proportion of treated patients with confirmed clinical response and no CDAD recurrence through 30 days after the end of treatment, was higher for fidaxomicin than for vancomycin (68.4% vs. 50.0% with a 95% CI for the treatment difference of 18.4 [1.5%, 35.3%]).

The safety of fidaxomicin in pediatric patients 6 months to less than 18 years of age was evaluated in a phase 2 study which included 38 patients. In a phase 3 randomized, active-controlled trial, 98 patients were assigned to treatment with fidaxomicin and 44 patients were treated with vancomycin.

Treatment discontinuation due to adverse reactions occurred in 7.9% (3 of 38) of patients in the phase 2 trial, and in 1% (1 of 98) and 2.3% (1 of 44) of fidaxomicin and vancomycin-treated patients, respectively, in the phase 3 trial.

The most common selected adverse reactions, which occurred in ≥5% of pediatric patients treated with fidaxomicin in the phase 3 trial, were pyrexia (13.3%), abdominal pain (8.2%), vomiting (7.1%), diarrhea (7.1%), constipation (5.1%), increased aminotransferases (5.1%) and rash (5.1%).

One death occurred in the phase 2 single-arm trial and 3 deaths occurred in the phase 3 trial of fidaxomicin-treated patients. All deaths were in children under 2 years and were reported to be related to underlying comorbidities. No deaths occurred in vancomycin-treated patients during the study period.

The supplemental new drug applications for both new indications were accepted for review on October 2, 2019. The antibiotic has been approved for use in adults since 2011. An investigational pediatric indication for fidamoxicin was granted Orphan Drug Designation in 2010.

Fidamoxicin is not effective for the treatment of other types of infection due to minimal systemic absorption and should only be used for cases of C diff infection.