Allergan plc announced the US Food and Drug Administration (FDA) has accepted for filing the company's supplemental New Drug Application (sNDA) for Teflaro (ceftaroline fosamil). If approved, this filing will expand the label of Teflaro beyond adults to include the treatment of children two months of age and older with acute bacterial skin and skin structure infections (ABSSSI) including infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and community-acquired bacterial pneumonia (CABP) caused by Staphylococcus pneumoniae and other designated susceptible bacteria.
"The impact of ABSSSI and CABP are significant among children, particularly those under the age of five who are often hospitalized due to these infections. This acceptance brings us one step closer to providing another choice for physicians to properly treat pediatric patients with ABSSSI and CABP, including those infections caused by difficult-to-treat pathogens," said David Nicholson, executive vice president & president, global brands research and development, Allergan. "We remain committed to the research and development of Teflaro and our entire anti-infective portfolio to improve care and treatment of patients who have limited FDA approved options for these types of infections."
This application was based on results from five clinical studies evaluating Teflaro in pediatric patients, including one active-controlled study in subjects with ABSSSI, two active-controlled studies in pediatric patients with CABP and two pharmacokinetic (PK) studies. In the ABSSSI active-controlled study the efficacy and safety of Teflaro were compared with vancomycin or cefazolin with or without aztreonam. In the CABP studies, Teflaro was compared with ceftriaxone or ceftriaxone plus vancomycin.
In the ABSSSI paediatric trial, the clinical response at study day 3, as measured by cessation of lesion spread and absence of fever, was 80.4 percent (86/107) in patients treated with Teflaro and 75 percent (39/52) for the comparator group.
The CABP pediatric trials evaluated the efficacy and safety of two separate dosing regimens of Teflaro. In the trial submitted for this pediatric filing, the clinical response at study day 4, as measured by 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) as well as by no worsening of these symptoms, was 69.2 percent (74/107) for patients treated with Teflaro and 66.7 percent (24/36) in the comparator group.
Teflaro was first approved by the US FDA in October 2010 for the treatment of adults with CABP and ABSSSI due to designated susceptible pathogens. Teflaro is a bactericidal cephalosporin with activity against both Gram-positive and Gram-negative pathogens. Teflaro is indicated for the treatment of CABP, including cases caused by Streptococcus pneumoniae, and ABSSSI, including cases caused by methicillin-resistant Staphylococcus aureus (MRSA). Teflaro is the first and only cephalosporin with activity against MRSA. In clinical trials, Teflaro was generally well-tolerated with an adverse event profile consistent with the cephalosporin class of antibiotics. Teflaro has been administered in over 2.3 million days of therapy, treating more than 350,000 patients.
Allergan plc (formerly Forest Laboratories) obtained the worldwide rights (excluding Japan, where Takeda Pharmaceuticals holds rights) to Teflaro in 2007 when it acquired Cerexa, Inc., a privately held biopharmaceutical company. In August 2009, Forest Laboratories and AstraZeneca entered into a definitive collaboration agreement to co-develop and commercialize ceftaroline fosamil in all markets outside the US, Canada and Japan.
In the four pooled phase 3 clinical trials, serious adverse reactions occurred in 98/1300 (7.5 per cent) of patients receiving Teflaro and 100/1297 (7.7 per cent) of patients receiving comparator drugs. Treatment discontinuation due to adverse reactions occurred in 35/1300 (2.7 per cent) of patients receiving Teflaro and 48/1297 (3.7 per cent) of patients receiving comparator drugs with the most common adverse reactions leading to discontinuation being hypersensitivity for both treatment groups at a rate of 0.3 per cent in the Teflaro group and 0.5 per cent in the comparator group.
No adverse reactions occurred in greater than 5 per cent of patients receiving Teflaro. The most common adverse reactions occurring in >2 per cent of patients receiving Teflaro in the pooled phase 3 clinical trials were diarrhea, nausea, and rash.
In 2014, there were 2.7 million hospital admissions for ABSSSI, of which 11 percent were for pediatric patients, which included patients with cellulitis, erysipelas, wound infection and major cutaneous abscess. The majority of all skin and soft tissue infections in hospitalized patients are caused by streptococci and Staphylococcus aureus, and approximately 59 percent of these Staphylococcus aureus infections in the U.S. are estimated to be caused by MRSA. Early and effective treatment of ABSSSI is critical to optimize patient recovery and for certain patients may also help to avoid potentially lengthy and costly hospital stays.
In 2014, there were 1.3 million hospital admissions for CABP, of which 8 percent were for pediatric patients. While the overall incidence of pneumonia is declining, it is still a leading cause of mortality accounting for more than 50,000 deaths in 2013. The cost of care for patients with CABP in the US has been estimated to be more than $10 billion annually.