The U.S. Food and Drug Administration (FDA) has rejected applications requesting the approval of oral and intravenous Solithera (solithromycin) to treat community-acquired bacterial pneumonia (CABP) in adults, recommending instead a new and larger clinical study to better assess the drug’s safety, its developer, Cempra, announced in a release.
In its Complete Response Letter to the company, the FDA stated the applications were not acceptable in their current form, noting that more information was needed relating to “clinical safety information and the satisfactory resolution of manufacturing facility inspection deficiencies” before they might be approved.
Specifically, the FDA determined that the risk of hepatotoxicity was inadequately characterized, because the safety database submitted pertained to 920 treated patients in clinical studies, a number “too small to adequately characterize the nature and frequency of serious hepatic [liver] adverse effects,” the release states.
The agency did not question the efficacy of Solithera in the treatment of CABP.
Solithera’s effectiveness and safety were tested in two Phase 3 clinical trials in CABP patients, one assessing the oral form of the drug candidate (NCT01756339, Solitaire-Oral) and the other the intravenous form (NCT01968733, Solitaire-IV). The formulas were found to be comparable to moxifloxacin, a commonly used antibacterial agent, the company announced in 2015.
Rather, the FDA recommended that Cempra consider initiating a new clinical study involving about 9,000 CABP patients to better evaluate Solithera’s safety profile, and “enable the exclusion” of serious drug-induced liver injury.
Problems were also noted during inspections of two manufacturing facilities, Wockhardt and Hospira, the FDA stated.
Cempra plans to meet with FDA representatives soon to discuss the issues highlighted in the response letter and begin to resolve them.
“As the rates of antibiotic resistance continue to rise, there is an unmet medical need for new antibiotics to treat patients with CABP and Cempra is committed to working with the FDA to achieve the approval of solithromycin [Solithera] as quickly as possible,” David Zaccardelli, Pharm.D. acting chief executive officer of Cempra, said in the company’s release.
“With more than $225 million of cash on hand, patent protection for solithromycin through 2032 and a pipeline that includes fusidic acid and other potential programs for solithromycin, including an ophthalmic formulation, we have flexibility to determine the best course forward for solithromycin and Cempra,” Zaccardelli added.
Solithera is also being evaluated in a Phase 3 clinical trial for uncomplicated urogenital urethritis.