Trials underway to evaluate solithromycin for gonorrhea, NASH

Solithromycin, a next-generation macrolide with activity against various strains of bacteria, will be assessed in two clinical trials as a potential drug candidate for urogenital gonorrhea and nonalcoholic steatohepatitis, according to a pair of press releases.

Previously, solithromycin (Cempra) was investigated among in vitro and in vivo studies and has shown “potent activity” against Streptococcus pneumoniae, and extended activity against CA-MRSA, streptococci, Haemophilus, enterococci and Mycobacterium avium, according to a release. In addition, data presented at IDWeek 2015 showed a 5-day regimen of oral solithromycin was noninferior to a 7-day regimen of moxifloxacin for the treatment of community-acquired bacterial pneumonia and performed as well as or better than moxifloxacin in the subgroup of patients who had identified Mycoplasma pneumoniae infection.

Solithromycin as a single oral dose agent against urogenital gonorrhea

Cempra recently launched a phase 3 trial, Solitaire-U, that will examine the safety and efficacy of solithromycin in patients with urogenital gonorrhea. To date, 250 patients, mostly men, from the U.S. and Australia have been enrolled in the trial. Through an agreement with the National Institute of Allergy and Infectious Diseases, Cempra will enroll 60 additional women and adolescents with confirmed gonorrhea. 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.

“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. “We are pleased that the NIAID will be expanding this study to enroll the additional patient populations that could eventually be included for the label indication, should solithromycin be approved for the treatment of urogenital gonorrhea. 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.”

Annual surveillance data from the CDC revealed large increases in nationally notifiable STD rates within the United States, with a record number of chlamydia cases reported in 2014. Reported gonorrhea cases (n = 350,062) resulted in a 5.1% rate increase to 110.7 cases per 100,000 population. In addition, the percentage of Neisseria gonorrhoeae isolates with reduced azithromycin susceptibility increased by 2.5%.

According to another press release, solithromycin is 8 to 16 times more potent than azithromycin and has activity against azithromycin-resistant strains.

“Solithromycin’s activity against resistant strains is driven by its ability to interact with three sites on the bacterial ribosome, compared to one for current macrolides,” the release said. “The binding to three ribosomal sites is expected to limit resistance development.”

If approved, solithromycin could offer a convenient oral treatment for patients with gonorrhea, the release said.

Immunomodulatory, anti-NASH activity observed with solithromycin

The safety of solithromycin also will be evaluated in patients with nonalcoholic steatohepatitis (NASH) without cirrhosis during a phase 2 trial, according to a press release.

Inflammation plays an important role in the progression of NASH, and 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. “There is a great need to develop medicines that target the hepatic inflammation caused by NASH and an effective immunomodulatory treatment may reduce disease progression.”

Up to 15 patients aged 18 to 70 years will be enrolled in the trial by the end of this year, according to the 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.

Disclosure: Fernandes reports being employed by Cempra.

Solithromycin, a next-generation macrolide with activity against various strains of bacteria, will be assessed in two clinical trials as a potential drug candidate for urogenital gonorrhea and nonalcoholic steatohepatitis, according to a pair of press releases.

Previously, solithromycin (Cempra) was investigated among in vitro and in vivo studies and has shown “potent activity” against Streptococcus pneumoniae, and extended activity against CA-MRSA, streptococci, Haemophilus, enterococci and Mycobacterium avium, according to a release. In addition, data presented at IDWeek 2015 showed a 5-day regimen of oral solithromycin was noninferior to a 7-day regimen of moxifloxacin for the treatment of community-acquired bacterial pneumonia and performed as well as or better than moxifloxacin in the subgroup of patients who had identified Mycoplasma pneumoniae infection.

Solithromycin as a single oral dose agent against urogenital gonorrhea

Cempra recently launched a phase 3 trial, Solitaire-U, that will examine the safety and efficacy of solithromycin in patients with urogenital gonorrhea. To date, 250 patients, mostly men, from the U.S. and Australia have been enrolled in the trial. Through an agreement with the National Institute of Allergy and Infectious Diseases, Cempra will enroll 60 additional women and adolescents with confirmed gonorrhea. 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.

“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. “We are pleased that the NIAID will be expanding this study to enroll the additional patient populations that could eventually be included for the label indication, should solithromycin be approved for the treatment of urogenital gonorrhea. 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.”

Annual surveillance data from the CDC revealed large increases in nationally notifiable STD rates within the United States, with a record number of chlamydia cases reported in 2014. Reported gonorrhea cases (n = 350,062) resulted in a 5.1% rate increase to 110.7 cases per 100,000 population. In addition, the percentage of Neisseria gonorrhoeae isolates with reduced azithromycin susceptibility increased by 2.5%.

According to another press release, solithromycin is 8 to 16 times more potent than azithromycin and has activity against azithromycin-resistant strains.

“Solithromycin’s activity against resistant strains is driven by its ability to interact with three sites on the bacterial ribosome, compared to one for current macrolides,” the release said. “The binding to three ribosomal sites is expected to limit resistance development.”

If approved, solithromycin could offer a convenient oral treatment for patients with gonorrhea, the release said.

Immunomodulatory, anti-NASH activity observed with solithromycin

The safety of solithromycin also will be evaluated in patients with nonalcoholic steatohepatitis (NASH) without cirrhosis during a phase 2 trial, according to a press release.

Inflammation plays an important role in the progression of NASH, and 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. “There is a great need to develop medicines that target the hepatic inflammation caused by NASH and an effective immunomodulatory treatment may reduce disease progression.”

Up to 15 patients aged 18 to 70 years will be enrolled in the trial by the end of this year, according to the 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.

Disclosure: Fernandes reports being employed by Cempra.