Fetroja (cefiderocol as sulfate tosilate)

The TGA assessed information from three studies that looked at the safety and effectiveness of Fetroja:

The APEKS-cUTI study

• This study included 448 people with complicated urinary tract infections, including kidney infections, caused by Gram-negative bacteria. Fetroja was compared with imipenem/cilastatin, an antibiotic already used to treat serious bacterial infections.
• The main outcome was assessed after treatment at the Test of Cure visit. At this visit, treatment was considered successful if a person’s symptoms had improved or had completely resolved and the bacteria causing the infection had been cleared or reduced to very low levels. 
• Fetroja achieved this combined outcome in 72.6% of people, compared with 54.6% of people who received imipenem/cilastatin. This showed that Fetroja worked at least as well as imipenem/cilastatin.
• Improvement in symptoms was similar in the two groups at the Test of Cure visit: 89.7% of people treated with Fetroja and 87.4% of people treated with imipenem/cilastatin had improved symptoms. The higher overall success rate with Fetroja was mainly because more people had the bacteria cleared: 73.0% with Fetroja compared with 56.3% with imipenem/cilastatin.

The CREDIBLE-CR study 

• This study included 150 adults with infections caused by carbapenem-resistant Gram-negative bacteria. The study included people with pneumonia acquired in hospital or while using a ventilator, bloodstream infections including sepsis, and complicated urinary tract infections.
• People in the study received either Fetroja or the best available treatment chosen by their doctor.
• Overall, Fetroja had similar clinical cure rates to the best available treatment at the Test of Cure visit. For people with hospital-acquired pneumonia, ventilator-associated pneumonia, healthcare-associated pneumonia, bloodstream infection or sepsis, cure rates were similar between the two treatment groups.
• For people with complicated urinary tract infections, the bacteria were cleared in 52.9% of people treated with Fetroja, compared with 20.0% of people who received the best available treatment.

The APEKS-NP study

• This study included 300 people with hospital-acquired pneumonia caused by Gram-negative bacteria. It compared Fetroja with high-dose meropenem, another antibiotic, in people with pneumonia acquired in hospital, while using a ventilator, or in a healthcare setting.
• The main aim was to compare how many people had died from any cause by Day 14 of treatment in the Fetroja group and the meropenem group.
• By Day 14, 12.4% of people in the Fetroja group and 11.6% of people in the meropenem group had died from any cause. Fetroja was found to be non-inferior to meropenem. This means it worked at least as well as meropenem based on the study’s pre-set criteria.
• At the Test of Cure visit, bacterial clearance and clinical cure rates were similar in the Fetroja and meropenem groups.

Across the three studies, Fetroja was generally well tolerated, although the total number of people studied was relatively small. Side effects were common, which was expected because many participants were seriously ill. 

In the CREDIBLE-CR study, deaths from any cause were more common in the Fetroja group (33.7%) than in the best available treatment group (18.4%). The increase in deaths in the Fetroja group was seen mainly in patients with infections caused by the Acinetobacter bacterial species. These deaths were not considered to be related to cefiderocol treatment, but the reason for the higher death rate was unclear. One possibility is that patients with Acinetobacter infection who received cefiderocol may have been more severely unwell at baseline, with a higher frequency of shock and admission to intensive care. Shock is a life-threatening condition where the body is not receiving enough blood flow and oxygen, and ICU admission generally indicates severe illness. These factors may have contributed to the difference in outcomes, but do not fully account for the increase in deaths in the Fetroja group. 

Side effects that were considered related to treatment tended to be less common with Fetroja than with the comparison treatment in each study.

Diarrhoea was more common with Fetroja than with the best available treatment in the CREDIBLE-CR study. However, diarrhoea occurred at a similar rate with Fetroja and meropenem in the APEKS-NP study, and was less common with Fetroja than with imipenem/cilastatin in the APEK`S-cUTI study.

Some people who received Fetroja had increases in liver enzymes. Increased liver enzymes in blood tests may indicate that the liver is irritated or under stress. These increases were usually mild or moderate and often had other possible causes, such as the person’s illness or side effects from other medicines. However, a small number of serious liver-related events were reported, so risk of liver injury cannot be ruled out completely.

Overall, the studies found that Fetroja had an acceptable safety profile. Diarrhoea and increases in liver enzymes were the main safety issues to monitor.

The TGA decided that the application provided enough evidence to support the quality, safety and effectiveness of Fetroja for the treatment of infections due to proven or strongly suspected carbapenem-resistant aerobic Gram-negative organisms in adults with limited treatment options, specifically complicated urinary tract infections (cUTIs), including pyelonephritis, hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia. The TGA determined that the medicine can be registered in Australia for these purposes.

More detailed information on why the TGA approved Fetroja will be published in the upcoming Australian Public Assessment Report (AusPAR).

For more information about possible side effects and risks, refer to the Consumer Medicine Information leaflet or Product Information document.

This decision summary will not be updated to reflect any subsequent changes and may therefore not contain the most current information about the medicine. For the latest information, refer to the medicine’s CMI or PI.