GAITHERSBURG, Md. – A Food and Drug Administration advisory panel voted 21 to 0 that the antimicrobial drug ceftaroline fosamil had been shown to be safe and effective for treating community-acquired bacterial pneumonia, based on the result of two clinical trials.
At a meeting of the FDA’s Anti-Infective Drugs Advisory Committee Sept. 7, panelists were enthusiastic about the drug, but had some concerns, including the lack of data in patients with methicillin-resistant Staphylococcus aureus (MRSA) since it’s likely the drug would be used to treat such infections. Another concern was the generalizability of the data, since the studies were done largely in Eastern European patients.
The manufacturer, Cerexa Inc., a subsidiary of Forest Laboratories Inc., has proposed that ceftaroline fosamil be approved for the treatment of adults with community-acquired bacterial pneumonia (CABP) or complicated skin and skin structure infections (cSSSI). The panel will discuss and vote on the cSSSI indication during the afternoon session of the meeting.
Ceftaroline, the active metabolite of ceftaroline fosamil, is a beta-lactam in the cephalosporin class of antimicrobials, with antibacterial activity against aerobic and anaerobic gram-positive and aerobic gram-negative bacteria, which are associated with skin and respiratory infections. The proposed dose for treating CABP is 600 mg administered intravenously every 12 hours, for 5-7 days, with a reduced dose for patients with moderate renal impairment.
In two international nearly identical phase III noninferiority studies of 1,240 patients with moderate to severe CABP, the effectiveness of treatment with ceftaroline at the proposed dose for 5-7 days was similar to treatment with the comparator, ceftriaxone (1 g IV every 24 hours). Effectiveness was based on the primary end point, clinical response at test of cure (TOC), 8-15 days after completing treatment. Clinical cure was defined as total resolution of all signs and symptoms of pneumonia or improvements to the extent that further antimicrobial treatment was not recommended. This end point was met by 84% and 81% of those treated with ceftaroline in the two studies, compared with 78% and 76% among those on the comparator, respectively. These results met the 10% noninferiority margin.
The safety profile of ceftaroline was similar to that expected for other cephalosporins, according to the company and FDA reviewers. The most common adverse reactions among those on ceftaroline were GI-related, such as diarrhea or nausea, followed by nervous system complaints such as headaches. The panelists also agreed that the safety profile was comparable to what would be expected with cephalosporins.