In cUTI, Fetroja demonstrated significantly higher efficacy vs high-dose imipenem/cilastatin at TOC1,2

Studied in a multinational, double-blind, non-inferiority trial vs imipenem-cilastatin in cUTI

Assessments1,2

Clinical trial assessment timeline Fetroja vs imipenem/cilastatin primary efficacy endpoint TOC 7 days post therapy ± 2 days Clinical trial assessment timeline Fetroja vs imipenem/cilastatin primary efficacy endpoint TOC 7 days post therapy ± 2 days
  • Non-inferiority study in patients with cUTI ┬▒ pyelonephritis (N=448)
  • Randomized 2:1 to receive Fetroja (n=300) or imipenem/cilastatin (n=148) for 7-14 days*
    • High dosage of imipenem/cilastatin used to allow for inclusion of patients with P aeruginosa infection
    • Carbapenem-resistant pathogens excluded as ethical necessity due to carbapenem comparator
  • Study was designed to capture a complicated patient population with comorbidities, who are at greater risk of multidrug-resistant Gram-negative infections
    • Allowed immunosuppressed patients, including renal transplant
    • Limited patients with acute uncomplicated pyelonephritis to 30% maximum
    • Step-down to oral therapy not permitted
* Dosages used were Fetroja 2 grams every 8 hours (infused over 1 hour), imipenem/cilastatin 1 gram/1 gram every 8 hours (infused over 1 hour).
Recommended dosing of Fetroja is 2 grams every 8 hours by intravenous (IV) infusion over 3 hours in patients with creatinine clearance (CLcr) ≥60 to <120 mL/min.1

Primary endpoint

Primary endpointa: Composite clinical responseb and Microbiological eradicationc at TOC1,2

Fetroja 72.6 % (n=183/252); Imipenem/cilastatin 54.6% (n=65/119); Treatment difference 18.6% (95% CI, 8.2, 28.9) P=0.0004

CI=confidence interval; TOC=test of cure, 7±2 days after last dose of study drug.


Fetroja demonstrated significantly higher response rates vs high-dose imipenem/cilastatin in cUTI1

See Fetroja clinical data in HABP/VABP

Secondary endpointsa

Secondary endpointsa: TOC1

Microbiological eradicationc at TOC

Fetroja 73.0% (n=184/252); Imipenem/cilastatin 56.3% (n=67/119); Treatment difference 17.3% (95% CI, 6.9, 27.6)

Clinical responseb at TOC

Fetroja 89.7% (n=226/252); Imipenem/cilastatin 87.4% (n=104/119); Treatment difference 2.4% (95% CI, -4.7, 9.4)

Secondary endpointsa: Follow-up3

  • Composite of microbiological eradication and clinical response at follow-up: Fetroja 54.4% (n=137/252) vs imipenem/cilastatin 39.5% (n=47/119)
  • Treatment difference was 15.31% (95% CI, 4.69, 25.92)

Microbiological eradicationc at follow-up

Fetroja 57.1% (n=144/252); Imipenem/cilastatin 43.7% (n=52/119); Treatment difference 13.92% (95% CI, 3.21, 24.63)

Clinical responseb at follow-up

Fetroja 81.3% (n=205/252); Imipenem/cilastatin 72.3% (n=86/119); Treatment difference 9.02% (95% CI, -0.37, 18.41)

Subgroup analyses

Subgroup analysis of composite endpoint by baseline pathogens1†
Baseline Pathogen Subgroup Fetroja % (n/N) Imipenem/cilastatin % (n/N)
E coli 74.3%
(113/152)
57.0%
(45/79)
K pneumoniae 75.0%
(36/48)
48.0%
(12/25)
P mirabilis 76.5%
(13/17)
0.0%
(0/2)
P aeruginosa 44.4%
(8/18)
60.0%
(3/5)
E cloacae complex 61.5%
(8/13)
100.0%
(3/3)
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Patients may have been infected with more than one pathogen in the baseline urine culture.

Efficacy in subgroups was consistent with results in the overall population2

Subgroup analysis of composite endpoint at TOC in micro-ITT populationa
Treatment differences across subgroups by analysis population, age, sex, clinical diagnosis
4 patients had NDM-producing organisms in the Fetroja group; all 4 achieved clinical cure, with 3 also having eradication at TOC4

Among ESBL-producing pathogens at baseline, Fetroja achieved response in 62.9% (N=70) of patients vs 47.2% (N=36) for imipenem/cilastatin (16.66% treatment difference, 95% CI -3.08, 36.40) in composite endpoint at TOC2

Adverse reactions

Fetroja adverse reactions vs imipenem/cilastatin in cUTI1

Serious adverse reactions and adverse reactions leading to discontinuation
Adverse reaction Fetrojaa
(n=300)
Imipenem/
cilastatinb
(n=148)
Serious adverse reactions 4.7% 8.1%
Death 0.3% 0%
Discontinuation of treatment due to adverse reaction 1.7% 2.0%
In patients who received Fetroja, discontinuation of treatment due to adverse reaction included diarrhea (0.3%), drug hypersensitivity (0.3%), and increased hepatic enzymes (0.3%).
Selected adverse reactions occurring in ≥2% of patients receiving Fetroja in the cUTI trial
Diarrhea 4% 6%
Infusion site reactionsc 4% 5%
Constipation 3% 4%
Rashd 3% <1%
Candidiasise 2% 3%
Cough 2% <1%
Elevations in liver testsf 2% <1%
Headache 2% 5%
Hypokalemiag 2% 3%
Nausea 2% 4%
Vomiting 2% 1%
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a 2 grams IV over 1 hour every 8 hours (with dosing adjustment based on renal function).
b 1 gram IV over 1 hour every 8 hours (with dosing adjustment based on renal function and body weight).
c Infusion site reactions include infusion site erythema, inflammation, pain, pruritus, injection site pain, and phlebitis.
d Rash includes rash macular, rash maculopapular, erythema, skin irritation.
e Candidiasis includes oral or vulvovaginal candidiasis, candiduria.
f Elevations in liver tests include alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, blood alkaline phosphatase, hepatic enzyme increased.
g Hypokalemia includes blood potassium decreased.