FDA rejects approval of Nabriva’s Contepo over manufacturing concerns

The FDA rejected approval of a new antibiotic for the treatment of complicated UTIs, or cUTIs, due to issues related to facility inspections and manufacturing deficiencies, according to a news release.

Contepo (IV fosfomycin, Nabriva Therapeutics) — previously referred to as ZTI-01 and Zolyd — is an investigational, first-in-class, epoxide antibiotic with broad-spectrum activity against gram-negative and gram-positive pathogens, including most contemporary multidrug-resistant strains, according to the company.

In the release, Nabriva said the issues raised by the FDA pertain to one of the company’s contract manufacturers. It said the agency did not request any new clinical data and did not raise any concerns about the safety of the antibiotic.

Nabriva said it would request a meeting to discuss the FDA’s findings.

“We will be working with the FDA in the coming weeks to gain a full understanding of the FDA’s comments, with the goal of bringing this important treatment to patients as quickly as possible,” Nabriva CEO Ted Schroeder said in the release.

Recently published results from the phase 2/3 ZEUS trial showed that IV fosfomycin effectively treated cUTIs, including acute pyelonephritis, compared with IV piperacillin-tazobactam in hospitalized adults.

“Resistant cUTIs are rapidly emerging as a serious health threat for hospitalized patients, especially those with hospital-acquired infections or who do not respond to first-line antibiotic therapy,” Infectious Disease News Editorial Board member Keith S. Kaye, MD, MPH, professor of medicine at the University of Michigan Medical School and chair of the data monitoring committee for the ZEUS trial, said.

Nabriva said it would not comment further on the FDA’s decision. Before the announcement, Schroeder noted that IV fosfomycin has been on the market in Europe for several decades “and has grown about 20% year over year.” He said the pending approval would be a good step forward in the goal to develop much needed new antibiotics but would not be the final answer.

“We need more antibiotics and more antibiotics that work differently,” he told Infectious Disease News. “We’re all aware of the scary rise in bacterial resistance and it wasn’t that many years ago when infectious diseases leaders declared we had [won] the war on bugs, but the bugs kept evolving and evading what we had.

“If you keep throwing the same mechanism at the same bacteria over and over again, eventually the survivors evolve and find their way around the antibiotics. Having new ways to kill gives you a fresh start. With a new class, you’re starting fresh and coming at the bacteria a different way.”– by Caitlyn Stulpin

Disclosures: Kaye is a member of the data monitoring committee and a consultant to Zavante Therapeutics, which is now part of Nabriva. Schroder is the CEO of Nabriva Therapeutics.