The FDA has approved a supplemental new drug application (sNDA) for ceftaroline fosamil (Teflaro, Allergan), granting new indications for pediatric patients 2 months of age to less than 18 years of age with acute bacterial skin and skin-structure infections (ABSSSIs), including infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and community-acquired bacterial pneumonia (CABP) caused by Streptococcus pneumoniae and other designated susceptible bacteria.
Ceftaroline is a bactericidal cephalosporin with activity against both gram-positive and gram-negative pathogens.
The new indications were approved based on results from clinical studies evaluating ceftaroline in pediatric patients (2 months to less than 18 years of age), including one active-controlled study in ABSSSI and two active-controlled studies in CABP. In the ABSSSI active-controlled study, the efficacy and safety of ceftaroline were compared with that of vancomycin or cefazolin (each with optional aztreonam). In the CABP studies, ceftaroline was compared with ceftriaxone. The use of ceftaroline in pediatric patients 2 months to less than 18 years of age is supported by evidence from studies of ceftaroline in adults, as well as additional pharmacokinetic and safety data from pediatric trials.
The primary objective of the pediatric ABSSSI and CABP studies was to evaluate the safety and tolerability of ceftaroline. These studies were not powered for a comparative inferential efficacy analysis, and no efficacy endpoints were identified as primary.
To evaluate the treatment effect of ceftaroline in the ABSSSI pediatric trial, an analysis was conducted in 159 patients in the modified intent-to-treat (mITT) population. This analysis evaluated responder rates based on achieving both cessation of lesion spread and absence of fever on day 3.
Patients treated with ceftaroline showed a higher response at day 3 compared with the comparator group, with a clinical response achieved in 80% (86/107) of patients treated with ceftaroline and in 75% (39/52) of patients in the comparator group. Clinical cure rates at the test-of-cure (TOC) visit (eight to 15 days after the end of therapy) in the ABSSSI pediatric trial were 94% (101/107) for patients treated with ceftaroline and 87% (45/52) for the comparator group.
To evaluate the treatment effect of ceftaroline in the CABP trial submitted for the new pediatric filing, an analysis was conducted in 143 patients with CABP in the mITT population. This analysis evaluated responder rates at day 4 based on achieving improvement in at least two out of seven symptoms (cough, dyspnea, chest pain, sputum production, chills, feeling of warmth/feverish, and exercise intolerance or lethargy), and worsening in none of these symptoms.
The clinical response at day 4 was 69% (74/107) for patients treated with ceftaroline and 67% (24/36) for the comparator group. Clinical cure rates at TOC were 88% (94/107) for patients treated with ceftaroline and 89% (32/36) for the comparator.
Ceftaroline fosamil was first approved by the FDA in October 2010 for the treatment of adults with CABP and ABSSSI due to designated susceptible pathogens. Ceftaroline is now indicated in adult and pediatric patients 2 months of age and older for the treatment of CABP, including cases caused by S. pneumoniae, and ABSSSI, including cases caused by MRSA. It is the only cephalosporin with activity against MRSA in ABSSSI. In clinical trials, ceftaroline was generally well tolerated, with an adverse event profile consistent with that of the cephalosporin class of antibiotics.
Source: Allergan; May 31, 2016