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FETCROJA (cefiderocol)

Opinions on drugs - Posted on Jan 26 2021

Reason for request

First assessment

Key points

Favourable opinion for reimbursement in the MA indication only as a last resort for the treatment of patients with infections due to multiresistant Gram-negative bacteria (particularly in the event of Enterobacterales and Pseudomonas aeruginosa, with a KPC, oxacillinase or metallo-β-lactamase resistance mechanism [NDM, VIM, IMP]) and when the use of the other available options is not possible.

Unfavourable opinion for reimbursement in other situations.

What therapeutic improvement?

Therapeutic improvement in management.

Role in the care pathway?

In June 2019, the HAS published guidelines relating to the antibiotic treatment of Enterobacterales and Pseudomonas aeruginosa infections in adults, specifying the role of carbapenems and their alternatives.

Role of the medicinal product in the care pathway

FETCROJA (cefiderocol) is a last-resort antibiotic reserved for patients with infections due to multiresistant Gram-negative bacteria (particularly in the event of Enterobacterales and Pseudomonas aeruginosa, with a KPC, oxacillinase or metallo-β-lactamase resistance mechanism [NDM, VIM, IMP]), with the exception of Acinetobacter baumannii and Stenotrophomonas maltophilia.

FETCROJA (cefiderocol) should not be used as an alternative to carbapenems for the treatment of third-generation cephalosporin-resistant Enterobacterales and for the treatment of carbapenem-susceptible P. aeruginosa infections.

The use of this antibiotic should only be considered as a last resort, i.e. when the other available options are not possible.

The Committee specifies that, despite the favourable response observed in studies, the uncertainties related to the higher mortality observed with cefiderocol in the CREDIBLE-CR study, which currently remains unexplained, particularly in the event of pneumonia, bacteraemia and/or sepsis due to Acinetobacter baumannii, mean that it is not possible to reach a conclusion with respect to the benefit of this antibiotic in the event of infection caused by this microorganism. In addition, the clinical efficacy has not been established in Stenotrophomonas maltophilia infections (only 5 patients in the CREDIBLE-CR study). The Committee would like to have additional data.

It should not be used as probabilistic treatment but solely on the basis of microbiological documentation.

Special recommendations

Given the product characteristics and the need to restrict its use to a last-resort treatment only in order to preserve it, the decision to initiate treatment with FETCROJA (cefiderocol) should be taken following a documented proposal based on a treatment review meeting with an antibiotic expert, with systematic reassessment 48 hours after the start of treatment.

The Committee is awaiting additional data from the pharmaceutical company in order to better assess the clinical value of cefiderocol in the event of infections due to non-fermenter bacteria, such as Acinetobacter baumannii and Stenotrophomonas maltophilia. Depending on the content of this data, the Committee may revise its opinion.

 


Clinical Benefit
Substantial

The Committee deems that the clinical benefit of FETCROJA (cefiderocol) is substantial only as a last resort for the treatment of patients with infections due to multiresistant Gram-negative bacteria (particularly in the event of Enterobacterales and Pseudomonas aeruginosa, with a KPC, oxacillinase or metallo-β-lactamase resistance mechanism [NDM, VIM, IMP]) and when the use of the other available options is not possible.
Insufficient

The Committee deems that the clinical benefit of FETCROJA (cefiderocol) is insufficient to justify public funding cover in other clinical situations, including infections with Acinetobacter baumannii or Stenotrophomonas maltophilia, pending additional data.

Clinical Added Value
minor

Considering:

  • its in vitro activity on a broad variety of Gram-negative bacteria, such as Enterobacterales and Pseudomonas aeruginosa, with a KPC, oxacillinase or metallo-β-lactamase resistance mechanism [NDM, VIM, IMP] or non-fermenter bacteria such as Acinetobacter baumannii orStenotrophomonas maltophilia,
  • the fact that cefiderocol is one of the few current antibiotics active against these microorganisms,
  • the results of 2 clinical studies demonstrating its efficacy in terms of non-inferiority compared to the imipenem/cilastatin combination in the treatment of urinary tract infections on microbiological eradication (APEKS-cUTI study) and compared to high-dose meropenem in the treatment of nosocomial pneumonia on all-cause mortality (APEKS-NP study), due to carbapenem-sensitive Gram-negative bacteria,
  • the limited clinical data in situations where the other therapeutic options have been exhausted (CREDIBLE-CR study) suggesting a favourable response in terms of clinical recovery and microbiological eradication in patients with carbapenem-resistant infections, particularly those with a metallo-β-lactamase resistance mechanism for whom few or no alternatives are available,
  • the need to have access to new antibiotics with improved efficacy, safety and resistance profiles,

But:

  • a higher mortality observed in the CREDIBLE-CR study, which is still unexplained, particularly in the event of pneumonia, bacteraemia and/or sepsis due to Acinetobacter baumannii and limited data in Stenotrophomonas maltophilia infections,
  • pending additional data enabling better assessment of the therapeutic contribution of cefiderocol in the event of infection with non-fermenter bacteria such as Acinetobacter baumannii or Stenotrophomonas maltophilia,

The Committee considers that FETCROJA (cefiderocol) provides a minor clinical added value (CAV IV) in the treatment of patients with infections due to multiresistant Gram-negative bacteria (particularly in the event of Enterobacterales and Pseudomonas aeruginosa, with a KPC, oxacillinase or metallo-β-lactamase resistance mechanism [NDM, VIM, IMP]) and when the use of the other available options is not possible.

 

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