February 10, 2016
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Oral solithromycin noninferior to oral moxifloxacin for pneumonia

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Recent results from a phase 3 multicenter trial indicate a 5-day regimen of oral solithromycin may be clinically noninferior to a 7-day regimen of oral moxifloxacin for the treatment of community-acquired bacterial pneumonia.

In addition, solithromycin (CEM-101, Cempra), a next-generation macrolide, appeared to have a similar safety profile to moxifloxacin and could offer providers an alternative to the β-lactam and fluoroquinolone-based treatment strategies currently employed, Carlos M. Barrera, MD, pulmonologist and endocrinologist at South Miami Hospital of Baptist Health Miami, and colleagues wrote.

Carlos M. Barrera, MD

Carlos M. Barrera

“Pneumonia is still the number eight [cause of] mortality in the United States and other developed countries, so it’s not a small problem,” Barrera told Infectious Disease News. “Resistance problems among antibiotics is something that is getting worse over time — it’s an inevitable process. To have a new antibiotic with no resistance … it’s an important addition to the armamentarium of the physician.”

Comparable efficacy, safety profile

In the double-blind, randomized, active-controlled, noninferiority trial, Barrera and colleagues recruited 860 adult patients with clinically- and radiographically-confirmed pneumonia from 114 health care centers around the globe between Jan. 3, 2013 and Sept. 24, 2014. Participants who received systemic antibacterial treatment for their current illness within the previous 7 days were excluded, along with those with recent hospital or health care facility admission, immunosuppression and drug-related factors.

The researchers randomly assigned participants to receive either a once-daily oral moxifloxacin regimen for 7 days, or once-daily oral solithromycin for 5 days and placebo for 2 days. Patients were screened from baseline until 4 or 5 weeks after treatment initiation, and adherence was assessed by pill counts during visits. The primary outcome was early clinical response based on symptoms, with others including clinical success and the incidence of adverse events.

Within the intention-to-treat population, 78.2% of patients in the solithromycin group and 77.9% of patients in the moxifloxacin group had an early clinical response (absolute difference, 0.29%; 95% CI, –5.5 to 6.1), the researchers wrote, suggesting that each treatment was similarly effective in achieving the primary endpoint. No significant differences were observed in clinical success rates or the proportion of participants who were clinically evaluable for analysis.

Safety profiles were also similar between the groups, as 10% of the solithromycin group and 13% of the moxifloxacin group experienced treatment-emergent adverse events. These were most often mild, with gastrointestinal disorders, such as diarrhea, nausea and vomiting, and nervous system disorders, including headache and dizziness, being the most frequent.

Also of note was the wide range of pathogens effectively treated by solithromycin, Barrera said, and the potential for a new treatment able to circumvent the various resistances prevalent among these bacteria.

“You now have available to you a monotherapy drug with a 5-day treatment that you can treat mild to severe pneumonia,” Barrera said. “A drug that has no resistance, and has such wide coverage, is a very important finding.”

The FDA has granted Fast Track designation for solithromycin IV and capsules for community-acquired bacterial pneumonia. In a press release, Cempra said that it intends to submit a New Drug Application for both formulations sometime during the first half of 2016.

Gonorrhea, NASH trials underway

Other trials to assess solithromycin treatment against urogenital gonorrhea and nonalcoholic steatohepatitis (NASH) are also currently underway, according to a pair of press releases.

Recently launched is a phase 3 trial, Solitaire-U, that will examine the safety and efficacy of solithromycin in patients with urogenital gonorrhea. According to release, 250 patients, mostly men, from the United States and Australia have been enrolled in the trial. Through an agreement with the National Institute of Allergy and Infectious Diseases, 60 additional women and adolescents with confirmed gonorrhea will be enrolled as well. Researchers will randomly assign patients to 1,000 mg solithromycin or the standard-of-care, 500 mg ceftriaxone administered intramuscularly and 1,000 mg oral azithromycin, and evaluate the results.

“There is a tremendous need for an effective, single-dose, oral treatment such as solithromycin that can provide coverage for both gonococcus and chlamydia for the entire population at risk for these infections,” Prabhavathi Fernandes, PhD, president and CEO of Cempra, said in a press release. “This potential use could be an attractive secondary market, in addition to the primary indication we are seeking for the treatment of community-acquired bacterial pneumonia.”

Up to 15 patients with NASH aged 18 to 70 years will be enrolled into another phase 2 trial by the end of this year, according to a release. The patients will receive two 200-mg capsules of solithromycin daily for 13 weeks. Along with assessing safety and tolerability, other primary endpoints include a change in liver histology via the Nonalcoholic Fatty Liver Disease Activity Score, fibrosis measurement, ballooning degeneration and markers of liver inflammation.

As inflammation plays an important role in the progression of NASH, the immunomodulatory and anti-NASH activity that has been observed with solithromycin in a murine diabetic NASH model may benefit patients, the release said.

“The commencement of this clinical trial represents an important potential step in furthering our understanding of solithromycin’s mechanism of action beyond antibacterial effects,” Fernandes said in the release. – by Dave Muoio

Disclosure: Barrera reports no relevant financial disclosures. Fernandes reports being employed by Cempra. Funding for these trials was provided by Cempra, and some researchers report employment or consultation with Cempra.