After positive panel vote, Shionogi antibiotic scores US approval
Safety concerns linked with Shionogi’s antibiotic were put to bed by an expert panel to the FDA, who largely voted to back the drug for complicated urinary tract infections (cUTI) last month. On Friday, the US regulator followed suit, granting the treatment official approval.
The drug, branded Fetroja, will be used in patients whose (cUTI) is suspected to have been caused by Gram-negative pathogens, which are increasingly growing resistant to standard therapies.
The tsunami of antibiotic resistance is an acute global threat. In the United States, at least 2.8 million people get an antibiotic-resistant infection each year, and more than 35,000 people die, according to a recent report by the CDC.
Shionogi’s marketing application largely relied on the results of the pivotal 448 hospitalized patient-APEKS-cUTI study — which tested its antibiotic against the broad spectrum regimen of imipenem/cilastatin. Data showed that 72.6% (183/252) of patients in the drug arm met the main composite goal of microbiological eradication and clinical response, versus 54.6% (65/119) in the comparator arm. The rate of serious side-effects were similar in type and rate between the two groups.
But in the open-label CREDIBLE-CR study, which investigated the efficacy and safety of the Shionogi antibiotic (which is known chemically as cefiderocol) versus best available therapy (BAT) in 150 patients with evidence of certain Gram-negative pathogens in patients with nosocomial pneumonia, bloodstream infections/sepsis, or cUTI — the rate of deaths on the Fetroja arm caused some concern.
There was a difference in all-cause mortality in 18 %, 24.8 %, and 33.7 % of cefiderocol-treated patients and 12.2 %, 18.4 %, and 18.4 % of BAT-treated patients at Day 14, Day 28, and end of study, respectively. An independent panel monitoring the study found that half of the patient deaths were the result of the patients’ underlying co-morbidity or infection complications other than the original Gram-negative infection for which the patient was randomized into the study.
Some members of the expert FDA panel expressed caution that the label should reflect the uncertainty with CREDIBLE-CR data. Overall, panelists voted 14-2 in favor of the drug, and the two voted against it suggested the compound should be further studied.
Fetroja — which is designed to penetrate the cell wall of Gram-negative bacteria subvert many of the resistance mechanisms that bacteria employ against antibiotics — will be made commercially available in early 2020, the Japanese drugmaker said on Thursday.
It is no secret that the industry players contributing to the arsenal of antimicrobials are fast dwindling. Drugmakers are enticed by greener pastures, compared to the long, arduous and expensive path to antibiotic approval that offers little financial gain as treatments must be priced cheaply, and often lose potency over time as microbes grow resistant to them.
The beleaguered field of antibiotics is desperate for a winner. For one of the biggest threats to global health, the lion’s share of antibiotic development is taking place in a handful of labs of small biopharma companies as a majority of their larger counterparts focus on more lucrative endeavors. In recent months, a handful of antibiotic developers — including Achaogen and Tetraphase — have seen their value go up in smoke as feeble drug sales frustrate growth. But on average, most freshly approved antibiotics have been more potent versions of existing classes of antibiotics.
Social image: Shionogi, Hiromitsu Morimoto via flickr