SUBGROUP ANALYSES

 

Therapeutic response was assessed with BLUJEPA vs NTF in subgroups of interest1-3

BLUJEPA demonstrated noninferiority* vs NTF in the overall patient population1

 

Trials: EAGLE-2 (N=1531) and EAGLE-3 (N=1605)—Phase 3, multicenter, randomized, parallel-group, double-blind, double-dummy, noninferiority clinical trials that compared BLUJEPA with nitrofurantoin (NTF) in the treatment of uUTIs.1

 

Primary endpoint: therapeutic response (success or failure)—Assessed in the microbiological intent-to-treat nitrofurantoin-susceptible (interim analysis set) population (micro ITT NTF-S [IA set]).1†

 

Treatment difference§ (BLUJEPA - NTF): 4.3%; 95% confidence interval [CI]: -3.6%, 12.1%1

Treatment difference§ (BLUJEPA - NTF): 14.6%; 95% CI: 6.4%, 22.8%1

See full trial details

  • *

    The Z statistic was used at the interim analysis to determine noninferiority. In both studies, the observed Z statistic exceeded the Z statistic boundary, indicating noninferiority to NTF. Noninferiority—Z statistic: EAGLE-2—observed 3.5554, boundary 2.065; EAGLE-3—observed 5.8838, boundary 2.098.1

     

  • †

    The micro ITT NTF-S (IA set) population: patients who were randomized, received ≥1 dose of study treatment, had 1 or 2 qualifying uropathogens (≥105 CFU/mL) at baseline that were susceptible to NTF, and, at interim analysis, had reached the test-of-cure visit or were known to not have attained therapeutic success before the test-of-cure visit.2

  • ‡

    Therapeutic success was defined as both clinical success (ie, total clinical symptom score for uncomplicated UTI of 0) and microbiological success (ie, reduction of qualifying bacterial uropathogens from ≥10⁵ CFU/mL at baseline to <10³ CFU/mL) without additional antibiotic use for uncomplicated UTI by test-of-cure. Treatment was considered therapeutic failure when these criteria were not met. Therapeutic failure also included patients with missing outcomes data and patients who had any other systemic antimicrobial use before the test-of-cure assessment.1

  • §

    Treatment difference (BLUJEPA - NTF) calculated using Miettinen-Nurminen Summary Score method adjusted for age group and recurrent/nonrecurrent infection status combinations.1

uUTI=uncomplicated urinary tract infection.

Subgroup analysis: therapeutic response in female patients with a history of recurrent uUTIs2

Results are descriptive only. No formal hypothesis test.

EAGLE-2 and EAGLE-3 therapeutic success charts in female patients with a history of recurrent uUTIs

Therapeutic success assessed at the test-of-cure visit in patients with a history of recurrent uUTIs‖ included in the microbiological ITT population who had NTF-susceptible isolates (complete data set).2

 

Treatment difference: BLUJEPA - NTF (unadjusted Miettinen-Nurminen method).2

‖History of recurrent uUTIs was defined as at least 1 previous patient-reported episode within 3 months before study entry, at least 2 previous episodes within 6 months before study entry, or at least 3 previous episodes within 12 months before study entry.1,2

 

NTF=nitrofurantoin; UTI=urinary tract infection; uUTI=uncomplicated urinary tract infection.

 

Learn more about patient characteristics when considering empiric uUTI treatment.

Jill has a uUTI and is at risk for empiric treatment failure due to her history of recurrent uUTIs.3

A woman with blonde hair in a gray sweater looking to the side against a blue background

Age: 38

Medical history: Has had 3 uUTIs in the past year and was fully adherent to her antibiotic treatment regimens. She is otherwise healthy.

Social history: Busy high school teacher. Coaches gymnastics. Avid bicyclist.

Subgroup analysis: therapeutic response in female patients >50 years old2

Results are descriptive only. No formal hypothesis test.

EAGLE-2 and EAGLE-3 therapeutic success charts in female patients over 50 years old

Therapeutic success assessed at the test-of-cure visit in women >50 years old included in the microbiological ITT population who had NTF-susceptible isolates (complete data set).2

 

**Treatment difference: BLUJEPA - NTF (unadjusted Miettinen-Nurminen method).2

 

NTF=nitrofurantoin; UTI=urinary tract infection; uUTI=uncomplicated urinary tract infection.

 

Learn about treatment failure risk among patients older than 50 years.

Kayla has a uUTI. She is over 50 and has recently been treated with an antibiotic; these are factors that put her at risk for failing empiric uUTI treatment.3

A woman with long dark hair, arms crossed, in a white blouse against a dark blue background

Age: 58

Medical history: Treated for a uUTI ~12 months ago and completed a full course of therapy. Received an antibiotic for an unrelated condition 4 months ago and was fully adherent to her antibiotic treatment. She is otherwise healthy.

Social history: Physical therapist and married. Attends water aerobics classes 4 times/week. Travels several times a year.

Subgroup analysis: therapeutic response in female uUTI subpopulations infected with antibiotic-resistant (including multidrug-resistant) E. coli 1,4

 

Results are descriptive only. No formal hypothesis test. Caution should be used when interpreting these results due to the small sample sizes and the limitation of subgroup analyses.

EAGLE-2: therapeutic success

 

  BLUJEPA
(n=336)		 NTF
(n=292)		 TREATMENT
DIFFERENCE††
E. coli‡‡ 51.1% (156/305) 45.9% (123/268)

5.3%

(CI:-3.0%, 13.4%)
  • ESBL+
 52.0% (26/50) 45.0% (18/40)

7.0%

(CI: -13.7%, 27.1%)
  • FQ-resistant
 47.9% (46/96) 38.5% (30/78)

9.5%

(CI: -5.4%, 23.8%)
  • TMP-SMX-resistant
 52.5% (42/80) 44.8% (30/67)

7.7%

(CI: -8.5%, 23.5%)
  • Multidrug-
    resistant§§
 51.1% (46/90) 44.3% (31/70)

6.8%

(CI:-8.8%, 22.0%)

EAGLE-3: therapeutic success

 

  BLUJEPA
(n=292)		 NTF
(n=275)		 TREATMENT
DIFFERENCE††
E. coli‡‡ 59.8% (156/261) 44.0% (111/252)

15.7%

(CI: 7.1%, 24.1%)
  • ESBL+
 55.9% (19/34) 28.0% (7/25) 27.9%
(CI: 2.1%, 49.8%)
  • FQ-resistant
 49.2% (32/65) 40.0% (20/50) 9.2%
(CI: -9.2%, 26.8%)
  • TMP-SMX-resistant
 56.3% (45/80) 43.1% (28/65) 13.2%
(CI: -3.2%, 28.9%)
  • Multidrug-
    resistant§§
 52.9% (37/70) 38.6% (22/57) 14.3%
(CI: -3.2%, 30.8%)

Therapeutic success assessed at the test-of-cure visit in patients with antibiotic-resistant uropathogens in the microbiological ITT population who had NTF-susceptible isolates (complete data set).1

  • ††

    Treatment difference: BLUJEPA - NTF (unadjusted Miettinen-Nurminen method).4

  • ‡‡

    Patients with >1 uropathogen of the same species were counted once.1

  • §§

    Multidrug resistance was defined as a uropathogen being resistant to ≥3 relevant antibacterial classes.2

E. coli=Escherichia coli; ESBL+=extended-spectrum beta-lactamase positive; FQ=fluoroquinolone; TMP-SMX=trimethoprim-sulfamethoxazole.

Learn about the efficacy of BLUJEPA

See the efficacy results from 2 clinical trials of BLUJEPA vs nitrofurantoin.

SEE EFFICACY DATA

Indication & Important Safety Info

Indication

Important Safety Information

Indication

BLUJEPA is indicated for the treatment of female adult and pediatric patients 12 years of age and older weighing at least 40 kilograms (kg) with uncomplicated urinary tract infections (uUTI) caused by the following susceptible microorganisms: Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii complex, Staphylococcus saprophyticus, and Enterococcus faecalis.

Usage to Reduce Development of Drug-Resistant Bacteria

To reduce the development of drug-resistant bacteria and maintain the effectiveness of BLUJEPA and other antibacterial drugs, BLUJEPA should be used only to treat infections that are proven or strongly suspected to be caused by bacteria.

Important Safety Information

CONTRAINDICATIONS

BLUJEPA is contraindicated in patients with a history of severe hypersensitivity to BLUJEPA.

WARNINGS AND PRECAUTIONS

QTc Prolongation

  • A dose and concentration-dependent prolongation of the QTc interval has been observed with BLUJEPA. Avoid use of BLUJEPA in patients with a history of QTc prolongation or with relevant pre-existing cardiac disease, patients taking antiarrhythmic agents, and in patients receiving drugs that prolong the QT interval. Due to an increase in BLUJEPA exposure, avoid concomitant administration of BLUJEPA with strong CYP3A4 inhibitors, in patients with severe hepatic impairment (Child-Pugh Class C), and in patients with severe renal impairment (estimated glomerular filtration rate [eGFR] <30 mL/min).

Acetylcholinesterase Inhibition

  • Dysarthria and other adverse reactions potentially attributed to acetylcholinesterase inhibition have been reported with BLUJEPA, an acetylcholinesterase inhibitor. Increased cholinergic effects can be associated with severe adverse effects, including atrioventricular block, bradycardia, bronchospasm, seizures/convulsions, and vasovagal syncope. Monitor patients with underlying medical conditions that may be exacerbated by acetylcholinesterase inhibition and patients receiving succinylcholine-type neuromuscular blocking agents, systemic anticholinergic medications, or non-depolarizing neuromuscular blocking agents.

Hypersensitivity Reactions

  • Hypersensitivity reactions, including anaphylaxis, have been reported in patients receiving BLUJEPA. If an allergic reaction to BLUJEPA occurs, discontinue the drug and institute appropriate supportive measures.

Clostridioides difficile-Associated Diarrhea

  • Clostridioides difficile infection (CDI) has been reported with nearly all systemic antibacterial agents, including BLUJEPA. Evaluate patients who develop diarrhea.
ADVERSE REACTIONS
  • The most common adverse reactions occurring in ≥1% of patients are diarrhea, nausea, abdominal pain, flatulence, headache, soft feces, dizziness, vomiting, and vulvovaginal candidiasis.
DRUG INTERACTIONS
  • CYP3A4 Inhibitors: Avoid coadministration of BLUJEPA with strong CYP3A4 inhibitors due to increased gepotidacin exposure.
  • CYP3A4 Inducers: Avoid coadministration of BLUJEPA with strong CYP3A4 inducers due to decreased gepotidacin exposure.
  • CYP3A4 Substrates: Avoid coadministration of BLUJEPA with drugs that are extensively metabolized by CYP3A4 and have a narrow therapeutic window.
  • Digoxin: Due to an increase in digoxin exposures, consider monitoring digoxin serum concentration, as appropriate, with concomitant administration of BLUJEPA.
USE IN SPECIFIC POPULATIONS
  • Renal Impairment: Avoid use of BLUJEPA in patients with severe renal impairment with eGFR <30 mL/min, including those receiving dialysis.
  • Hepatic Impairment: Avoid use of BLUJEPA in patients with severe hepatic impairment (Child-Pugh Class C).

Please see accompanying Prescribing Information, including Medication Guide, for BLUJEPA. 

To report SUSPECTED ADVERSE REACTIONS, contact GSK at gsk.public.reportum.com or 1-888-825-5249 or
FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

References

  1. Wagenlehner F, Perry CR, Hooton TM, et al. Oral gepotidacin versus nitrofurantoin in patients with uncomplicated urinary tract infection (EAGLE-2 and EAGLE-3): two randomised, controlled, double-blind, double-dummy, phase 3, non-inferiority trials. Lancet. 2024;403(10428):741-755. doi:10.1016/S0140-6736(23)02196-7

  2. Wagenlehner F, Perry CR, Hooton TM, et al. Oral gepotidacin versus nitrofurantoin in patients with uncomplicated urinary tract infection (EAGLE-2 and EAGLE-3): two randomised, controlled, double-blind, double-dummy, phase 3, non-inferiority trials. Supplementary appendix. Lancet. 2024;403(10428):1-33. doi:10.1016/S0140-6736(23)02196-7

  3. Fromer DL, Luck ME, Cheng WY, et al. Risk factors for treatment failure in US female outpatients with uncomplicated urinary tract infection: an observational study. J Gen Intern Med. 2024. doi:10.1007/s11606-024-09029-6

  4. Data on file, GSK.