In-house FDA review flags a suspicious imbalance in deaths as Shionogi hunts an OK for antibiotic
Shionogi has some big questions to answer if they plan to win an FDA panel’s backing for their new antibiotic.
While investigators have provided positive efficacy data for their new product to treat cases of complex urinary tract infections, an FDA review has flagged an imbalance of deaths between the antibiotic and a control arm — with a “higher mortality in cefiderocol-treated patients was observed in a trial in critically ill patients with a variety of infections due to carbapenem-resistant organisms.”
And they want the agency’s outside advisers to take a good hard look at that when they meet on Wednesday.
The antibiotic arm in question had a significant gap when researchers counted deaths, according to an internal review at the FDA.
The CREDIBLE-CR study was a descriptive study with no pre-specified hypothesis testing. The study completed enrollment during the NDA review; datasets were submitted to the Agency for review and the clinical study report was not submitted. In this trial, patients with HABP/VABP, cUTI, and BSI/sepsis due to carbapenem-resistant organisms were randomized to receive cefiderocol or BAT, of which 66% were colistin-based regimens. 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%).
Now an advisory committee will take that up on Wednesday before voting on whether or not the FDA should green light the new antibiotic at a time of rising drug resistance. Says the FDA: