MONTREAL – A new, next-generation macrolide, solithromycin, showed safety and efficacy as a once-daily oral agent that was noninferior to the comparator oral antibiotic, the fluoroquinolone moxifloxacin, in a phase III trial.
Macrolide resistance among strains of Streptococcus pneumoniae that cause many U.S. cases of severe community-acquired pneumonia has become common, complicating treatment of this common infection with a macrolide, Dr. Carlos M. Barrera explained at the annual meeting of the American College of Chest Physicians.
The SOLITAIRE-ORAL (Efficacy and Safety Study of Oral Solithromycin [CEM-101] Compared to Oral Moxifloxacin in Treatment of Patients With Community-Acquired Bacterial Pneumonia) trial enrolled 860 patients with moderate to moderately severe community-acquired pneumonia.
About half of the patients enrolled in the trial underwent microbiologic assessment of their infecting pathogen, and about 40% of cases in each treatment arm had infections caused by S. pneumoniae. In this subgroup, the 5-day regimen of solithromycin tested in the study succeeded in clearing the infection in 89% of patients, comparable to the 83% success rate achieved with a 7-day course of moxifloxacin (Avelox), said Dr. Barrera, a pulmonologist who practices in Miami.
The study’s primary endpoint for Food and Drug Administration approval of solithromycin was early clinical response, defined as an improvement in at least two listed symptoms at 72 hours after onset of treatment. That endpoint occurred in 78% of patients enrolled in each of the two arms of the study.
The data make solithromycin look like a promising way to once again have a macrolide available for empiric oral treatment of more severe community-acquired pneumonia, pending full peer review of the data, commented Dr. Muthiah P. Muthiah, a pulmonologist at the University of Tennessee Health Science Center in Memphis.
“A couple of decades ago, you could comfortably treat a patient with severe community-acquired pneumonia with a macrolide, but you can’t do that anymore,” Dr. Muthiah said in an interview.
If the newly reported data on oral solithromycin hold up under further review, it would mean that solithromycin was as effective as a potent quinolone, which remains an effective monotherapy for community-acquired pneumonia in patients who do not require treatment in an intensive care unit, Dr. Muthiah noted.
A companion study, SOLITAIRE-IV, is a phase III pivotal trial assessing the safety and efficacy of solithromycin when begun intravenously for treating community-acquired pneumonia, followed by a switch to oral dosing, in comparison with intravenous followed by oral treatment with moxifloxacin.
Once those data are fully collected and analyzed, the company will submit the information from both trials to the FDA, said Dr. David Oldach, chief medical officer for Cempra.
Results from the intravenous trial, reported in a preliminary way by Cempra Oct. 16 in a press release, showed that the solithromycin treatment regimen tested in SOLITAIRE-IV met its noninferiority targets, compared with moxifloxacin. The safety results, however, showed that solithromycin produced a higher number of patients with a liver-enzyme elevation, compared with patients treated with moxifloxacin.
In SOLITAIRE-IV, Cempra reported that grade 3 increase in levels of alanine transaminase (ALT) occurred in 8% of patients on solithromycin and in 3% of patients on moxifloxacin. Grade 4 increases in ALT occurred in less than 1% of patients in both treatment arms.
In the current, orally administered trial, grade 3 ALT increases occurred in 5% of patients treated with solithromycin and in 2% of patients treated with moxifloxacin, Dr. Barrera reported. Grade 4 ALT increases occurred in 0.5% of patients treated with solithromycin and in 1.2% of those treated with moxifloxacin. No patients in either arm developed an elevation of both ALT and bilirubin, and the ALT increases seen were reversible and asymptomatic, Dr. Barrera said.
By other assessments, the safety profiles of solithromycin and moxifloxacin were similar: 7% of patients on solithromycin and 6% on moxifloxacin had a serious adverse event, and 4% of patients in each study arm discontinued treatment because of an adverse event.
SOLITAIRE-ORAL was sponsored by Cempra, the company developing solithromycin. Dr. Barrera has received research funding from Cempra. Dr. Muthiah had no disclosures.
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