FDA says yes to Allecra, no to Venatorx UTI drugs

Approval and rejection

The FDA has approved Allecra Therapeutics' Exblifep, a combination antibiotic for complicated urinary tract infections (cUTIs) that will now launch later this year, but turned down a rival product from Venatorx.

The FDA has given the green light to Exblifep, based on long-established beta-lactam antibiotic cefepime and a new extended-spectrum beta-lactamase inhibitor (BLI) called enmetazobactam, for the treatment of cUTIs in adults, including severe kidney infections (acute pyelonephritis) caused by susceptible Gram-negative organisms.

Venatorx Pharmaceuticals and partner Melinta Therapeutics were not so fortunate with their application for cefepime with BLI taniborbactam in the same indication, getting a complete response letter (CRL) from the regulator with a request for more information on chemistry, manufacturing, and controls (CMC) for the drug.

Cefepime was first introduced in the 1990s, but has become increasingly ineffective against key resistant pathogens and was removed from the World Health Organization (WHO) list of essential medicines in 2019.

BLIs are designed to overcome a key resistance mechanism that allows pathogens to protect themselves from cefepime and other antibiotics in the beta-lactam class and have been used to restore activity against some ‘superbugs’, including Enterobacterales species and Pseudomonas aeruginosa resistant to carbapenems.

MSD took a similar approach with its Recarbrio (imipenem/cilastatin-relebactam) product, which was approved by the FDA for cUTIs and complicated intra-abdominal infections (cIAI) in 2019.

Exblifep’s approval was based on the ALLIUM study, which showed that the drug was superior to an older therapy based on piperacillin and tazobactam, achieving clinical cure and microbiological eradication in 79.1% and 58.9% of patients, respectively.

Allecra – which licenses enmetazobactam from Indian drugmaker Orchid Pharma – said the approval has unlocked a five-year marketing exclusivity extension from the FDA as part of the GAIN Act, which was passed to encourage the development of new anti-infectives and gives the drug patent protection in the US until 2032.

In Europe, the combination has been licensed to Advanz Pharma, which got a positive opinion for Exblifep from the EMA’s human medicines committee, the CHMP, at its January meeting.

Venatorx and Melinta, meanwhile, said that the CRL was a disappointment, but stressed that the FDA had not taken issue with the efficacy or safety data with cefepime-taniborbactam and had not asked for additional clinical testing.

Christopher Burns, Venatorx’s chief executive, said the two partners are “already hard at work generating the additional requested CMC data, and [...] will continue to work closely with the FDA so that [they] can make this important new medicine available to patients as quickly as possible.”

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