FDA Approves Merck’s Dificid for Pediatric Patients
The U.S. Food and Drug Administration (FDA) approved Merck’s Dificid (fidaxomicin) for a new oral suspension as well as for the treatment of Clostridioides difficile-associated diarrhea (CDAD) in children ages six months and older.
Dificid is a macrolide antibiotic that was previously approved for CDAD in adults.
“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,” said Larry K. Kociolek, associate medical director of Infection Prevention and Control at Ann & Robert H. Lurie Children’s Hospital of Chicago. “The fidaxomicin pediatric trial was the first randomized controlled trial of C. difficile infection treatment in children. I am very excited to have a new C. difficile infection treatment option for my pediatric patients.”
Clostridioides, previously called Clostridium difficile, is also known as C. diff or C. difficile. It is one of the most common causes of health care-associated infections in U.S. hospitals. The U.S. Centers for Disease Control and Prevention (CDC) estimate C. diff is the cause of about 500,000 infections each year in the U.S. and is linked to about 29,000 deaths within 30 days of initial diagnosis. The CDC’s Antibiotic Resistance Threats in the United States, 2019 report indicated that C. diff is an urgent threat that require urgent and aggressive action.
The approval for both the new formulation and new indication was built on a Phase III, multicenter, investigator-blind, randomized, parallel group study called SUNSHINE. The safety and efficacy of the drug was studied in children from six months to less than 18 years of age, although one patient was younger than six months old. The trial was sponsored by Astellas Pharma Europe with Merck & Co. as a collaborator. It included 148 randomized patients less than 18 years old with confirmed CDI. Of them, 142 were given either fidaxomicin suspension or tablet twice a day or vancomycin, suspension or tablets, four times a day in a 2:1 ratio.
In addition, the patients were randomized by age group. There were 30 patients ranging in age from 6 months to less than 2 years; 49 patients ages 2 to less than 6 years; 40 patients age 6 to less than 12 years; and 29 patients ranging from 12 years to less than 18 years.
CDAD clinical response overall was similar between the two groups at two days after 10 days of treatment, with 77.6% for the fidaxomicin group and 70.5% for the vancomycin group, with a 95% confidence interval (CI) for the treatment difference of 7.5. The sustained clinical response was higher for fidaxomicin than for vancomycin, 68.4% compared to 50%, with a 95% CI for the treatment difference of 18.4.
About 7.9% of patients discontinued treatment because of adverse reactions in the Phase II trial and 1% in the Phase III trial, with higher discontinuation rates in the vancomycin arms.
The company reports that there was one death in the Phase II single-arm trial and three deaths in the Phase III trial, all in Dificid-treated patients, none in the vancomycin-treated arms. However, all deaths were in patients less than 2 years of age and appeared to be linked to underlying health problems.
“C. difficile infection is an urgent public health challenge,” said Nicholas Kartsonis, senior vice president, clinical research, infectious diseases and vaccines, Merck Research Laboratories. “We are grateful to the health care practitioners, the patients and their families for their invaluable contributions in helping to bring this new pediatric indication and the oral suspension formulation for Dificid to the U.S. market.”