On 30 April, Nabriva Therapeutics announced that the US Food and Drug Administration (FDA) had issued a complete response letter (CRL) for its experimental antibiotic Contepo (fosfomycin) for treatment of complicated urinary tract infections Urethral Cancer Drugs Development market.
The rejection was largely unexpected, given the drug’s strong performance in a pivotal Phase II/III trial and Qualified Infectious Disease Product (QIDP) and fast track designations from the FDA.
The principal concern cited in the CRL were manufacturing deficiencies identified during facility inspections of one of Nabriva’s contract manufacturers.
Urinary tract infection antibiotics
Given the absence of requests for additional clinical data, GlobalData is confident that Contepo will eventually be licensed in the US market for the treatment of cUTIs, including acute pyelonephritis.
However, Nabriva now has limited room for error as it looks ahead to the upcoming FDA decision for its second experimental antibiotic, lefamulin, particularly given the commercial challenges within the global antibiotics market.
Contepo is a new formulation of intravenous fosfomycin, an established epoxide antibiotic that has been marketed for various infections in Europe for many years, with demonstrated broad-spectrum activity against both Gram-negative and Gram-positive bacteria.
The US new drug application (NDA) for Contepo follows positive results from the Phase II/III ZEUS trial, demonstrating an overall success rate of 64.7% for Contepo in cUTI versus 54.5% for the comparator piperacillin-tazobactam. Nabriva obtained rights to the drug relatively recently, through the acquisition of Zavante Therapeutics in 2018 for 8.2 million shares and around $100 million in milestone payments. In order to obtain a return on its sizable investment, the company is likely to pursue clinical testing in several other indications, including as combination therapy for multidrug-resistant infections.
Nabriva’s other late-stage drug, lefamulin, is a semi-synthetic pleuromutilin antibiotic slated for an FDA decision in August 2019. The NDA for lefamulin is supported by two pivotal, Phase III clinical trials (LEAP1/LEAP2) evaluating safety and efficacy of the drug compared with moxifloxacin in the treatment of adults with community-acquired bacterial pneumonia (CABP).
