Venatorx, Melinta's BARDA-funded antibiotic combo falls short with manufacturing-related rejection

As the World Health Organization and others pine for new innovation in antibiotics, a combination option from Venatorx Pharmaceuticals and Melinta Therapeutics won't be able to help out the cause anytime soon as manufacturing issues have led to an FDA rejection.

In a complete response letter, the agency requested further chemistry, manufacturing and controls (CMC) plus related data on the drug and its testing methods and manufacturing process, the companies disclosed in a Friday press release.

However, the FDA did not flag any safety or efficacy issues nor request new trials to support approval.

The antibiotic combines approved beta-lactam cefepime, which is branded by Pfizer as Maxipime, and Venatorx’s beta-lactamase inhibitor taniborbactam. The candidate scored both FDA fast track and qualified infectious disease product designations, the latter of which could potentially mean an additional five years of exclusivity.

“While we are disappointed with this setback, we maintain utmost confidence in cefepime-taniborbactam,” Venatorx CEO Christopher Burns, Ph.D., said in the release. “We are already hard at work generating the additional requested CMC data, and we will continue to work closely with the FDA so that we can make this important new medicine available to patients as quickly as possible.”

The partners were hoping to commercialize their beta-lactam/beta-lactamase inhibitor combination to treat complicated urinary tract infections (cUTIs). UTI complications include the kidney infection acute pyelonephritis, which happens when bacteria from the UTI moves from the bladder to the kidneys, as well as bacteria pneumonia that’s acquired after hospital admission and bacteria pneumonia that occurs following ventilation.

An estimated more than 3 million cUTI patients are diagnosed yearly and require antibiotic therapy that adds up to over $6 billion in annualized 30-day costs, according to the companies.  

Venatorx and Melinta originally linked up in November to commercialize cefepime-taniborbactam in the U.S. Meanwhile, Italy's Menarini Group has commercialization rights in 96 countries spanning Europe, Latin America, the Middle East, North Africa and other regions. Everest Medicines is responsible for development, registration and commercialization in China, South Korea and certain Southeast Asian countries.

Additional funding comes from the National Institute of Allergy and Infectious Diseases, the National Institutes of Health and the Department of Health and Human Services.

The Biomedical Advanced Research and Development Authority also has its hands on the project through a 2022 contract worth up to $318 million for the development and procurement of the combo for the treatment of multidrug-resistant infections and melioidosis. The partnership is an expansion of a previous agreement that funded a phase 3 trial of the combo. 

A phase 3 study of 661 adults with cUTIs saw 70% of participants achieving bacterial eradication and symptomatic clinical success, compared with 58% of patients on meropenem, an established beta-lactam antibiotic.