Despite worries triggered by imbalance of deaths, Shionogi's antibiotic clears FDA panel vote
Concerns over disproportionate mortality had not stopped a panel of experts to recommend that the FDA approve Shionogi’s antibiotic cefiderocol for complicated urinary tract infections, raising hopes of an OK next month.
After discussing the imbalance in deaths between the cefiderocol and control arms flagged by the agency’s in-house review, the majority of the Antimicrobial Drugs Advisory Committee voted in favor of the drug. More specifically, 14 agreed that there’s substantial evidence of efficacy and safety for cefiderocol in treating cUTI, while two voted against.
Back in 2017, Shionogi reported positive results from the APEKs-cUTI trial, where their new antibiotic cured 72.6% of patients compared to 54% in the imipenem/cilastatin arm. The study that the FDA’s reviewers took issue with was CREDIBLE-CR, which compared cefiderocol to best available therapy in a number of different infections caused by carbapenem-resistant Gram-negative pathogens.
From the internal docket released ahead of the ad comm:
All-cause mortality was higher in the cefiderocol group compared to the BAT group at Day 14 (18.8% versus 12.2%) and Day 28 (24.8% versus 18.4%) respectively. The greatest mortality difference disfavoring cefiderocol was noted in the HABP /VABP /HCABP subgroup, followed by the BSI/sepsis subgroup. An independent adjudication committee determined that a greater percentage of patients in the cefiderocol group than in the BAT group had infection-related death with treatment failure (15.8% vs. 8.2%), but also noted an imbalance in death due to underlying co-morbidities (9.9% vs. 4.1%).
3. Many committee members expressed opinions that the label needs to strongly note uncertainty associated with the CREDIBLE-CR data. The 2 members who voted no called for further study. " I know we need new drugs but we don’t need to feed the monster," one said.
— Michaela Fleming (@M_Fleming96) October 16, 2019
In a statement celebrating the outside experts’ endorsement, Shionogi president and CEO Isao Teshirogi highlighted the limited treatment options that are currently available for this group of patients.
“Patients with cUTIs caused by Gram-negative pathogens continue to face a serious challenge with high morbidity and mortality rates,” he said. “If approved, we believe cefiderocol could help address a significant unmet need in an area with limited treatment options to fight these life-threatening infections.”
The FDA is expected to make a decision by November 14 about the drug, which has been given the brand name Fetroja.