Merck, known as MSD outside the United States and Canada, today announced the U.S. Food and Drug Administration (FDA) has approved a New Drug Application (NDA) for DIFICID® (fidaxomicin) for oral suspension, and a supplemental New Drug Application (sNDA) for DIFICID tablets for the treatment of Clostridioides (formerly Clostridium) difficile-associated diarrhea (CDAD) in children aged six months and older.
DIFICID is a macrolide antibacterial medicine indicated in adults and pediatric patients aged 6 months and older for treatment of CDAD. To reduce the development of drug-resistant bacteria and maintain the effectiveness of DIFICID and other antibacterial drugs, DIFICID should be used only to treat infections that are proven or strongly suspected to be caused by Clostridioides difficile (C. difficile).
DIFICID is contraindicated in patients who have known hypersensitivity to fidaxomicin or any other ingredient in DIFICID. DIFICID should only be used for the treatment of CDAD. DIFICID is not expected to be effective for treatment of other types of infections due to minimal systemic absorption of fidaxomicin.
“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,” said Dr. Larry K. Kociolek, Associate Medical Director of Infection Prevention and Control at Ann & Robert H. Lurie Children’s Hospital of Chicago. “I am very excited to have a new C. difficile infection treatment option for my pediatric patients.”
“Merck is committed to developing new treatments, as well as expanding indications of existing ones, in order to provide more solutions to treat infectious diseases, particularly among children,” said Dr. Nicholas Kartsonis, senior vice president, clinical research, infectious diseases and vaccines, Merck Research Laboratories. “C. difficile infection is an urgent public health challenge. 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.”
Both applications received a priority review classification by the FDA. The investigational pediatric indication for DIFICID was granted Orphan Drug Designation in 2010.
The FDA’s approval of the new formulation and new indication for DIFICID was based on a Phase 3, multicenter, investigator-blind, randomized, parallel group study (known as the SUNSHINE study, NCT02218372), in which the safety and efficacy of fidaxomicin was evaluated in pediatric patients from 6 months to less than 18 years of age (one patient was less than six months of age).
This study, sponsored by Astellas Pharma Europe B.V. (with Merck & Co., Inc. as collaborator) included 148 randomized patients aged <18 years with confirmed CDI, 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, as follows: 30 patients from 6 months to <2 years; 49 patients age 2 to <6 years, 40 patients age 6 to <12 years and 29 patients age 12 to <18 years. Generally, the two treatment groups were balanced regarding demographics and other baseline characteristics. CDAD clinical response in the overall pediatric population, assessed through two days following 10 days of treatment, was similar between the fidaxomicin and vancomycin groups (77.6% vs. 70.5% with a 95% CI for the treatment difference of 7.5 [-7.4%, 23.9%]).
Sustained clinical response, defined as 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 DIFICID in pediatric patients 6 months to less than 18 years of age was evaluated in a Phase 2 single-arm trial in 38 patients and a Phase 3 randomized, active-controlled trial in 98 patients treated with DIFICID and 44 patients treated with vancomycin. Treatment discontinuation due to adverse reactions occurred in 7.9% (3/38) of patients in the Phase 2 trial, and in 1% (1/98) and 2.3% (1/44) of DIFICID- and vancomycin-treated patients, respectively, in the Phase 3 trial.
The most common selected adverse reactions occurring in ≥5% of pediatric patients treated with DIFICID 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 three deaths occurred in the Phase 3 trial of DIFICID-treated patients. No deaths occurred in vancomycin-treated patients during the study period (40 days). All deaths occurred in patients less than 2 years of age and appeared to be related to underlying comorbidities.
Clostridioides (formerly Clostridium) difficile, also known as C. difficile or C. diff, is one of the most common causes of health care-associated infections in U.S. hospitals.2 Recent estimates suggest C. difficile causes almost 500,000 infections annually in the United States and is associated with approximately 29,000 deaths within 30 days of initial diagnosis.3 According to the CDC’s Antibiotic Resistance Threats in the United States, 2019 (2019 AR Threats Report), C. difficile is categorized as an urgent threat and is stated as a public health threat that requires urgent and aggressive action.
Source: Company Press Release