Delving into the Latest Updates on Gepotidacin with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Gepotidacin (USAN/INN), Gepotidacin Mesylate, GSK 2140944

+ [4]

Target

Bacterial DNA gyrase x Bacterial top IV

Action

inhibitors

Mechanism

Bacterial DNA gyrase inhibitors(Bacterial DNA gyrase inhibitors), Bacterial top IV inhibitors(Bacterial topoisomerase IV inhibitors)

Therapeutic Areas

Infectious DiseasesUrogenital Diseases

Active Indication

Bacterial InfectionsUrinary Tract InfectionsAcute cystitis+ [3]

Inactive Indication

CellulitisErythema InduratumRespiratory Tract Infections

Originator Organization

GSK Plc

Active Organization

GSK PlcGlaxoSmithKline Trading Services Ltd.GlaxoSmithKline UK Ltd.

+ [1]

Inactive Organization

GlaxoSmithKline (China) Investment Co., Ltd.

Atos SE

License Organization-

Drug Highest PhaseApproved

First Approval Date

United States (25 Mar 2025),

Bacterial InfectionsUrinary Tract Infections

RegulationPriority Review (United States)

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Structure/Sequence

Molecular FormulaC24H28N6O3

InChIKeyPZFAZQUREQIODZ-LJQANCHMSA-N

CAS Registry1075236-89-3

A Phase III, Multicenter, Randomized, Active Reference, Double-blind, Double-dummy Study in Japanese Female Participants to Evaluate the Efficacy and Safety of Gepotidacin in the Treatment of Uncomplicated Urinary Tract Infection (Acute Cystitis) - A study to investigate the efficacy and safety with gepotidacin in Japanese female participants with uncomplicated urinary tract infection (acute cystitis); Efficacy of Antibacterial Gepotidacin Evaluated in Japan (EAGLE-J)

Start Date11 Jan 2023

Sponsor / Collaborator-

NCT05630833

/ CompletedPhase 3

A Phase III, Multicenter, Randomized, Active Reference, Double Blind, Double-dummy Study in Japanese Female Participants to Evaluate the Efficacy and Safety of Gepotidacin in the Treatment of Uncomplicated Urinary Tract Infection (Acute Cystitis)

The purpose of this study is to evaluate the consistency of therapeutic response of gepotidacin in female participants with acute uncomplicated cystitis with qualifying bacterial uropathogen(s) at baseline that all are susceptible to nitrofurantoin in Japan, with that from global studies (Studies 204989 [NCT04020341] and 212390 [NCT04187144]).

Start Date11 Jan 2023

Sponsor / Collaborator

GSK Plc

100 Clinical Results associated with Gepotidacin

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100 Translational Medicine associated with Gepotidacin

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100 Patents (Medical) associated with Gepotidacin

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101

Literatures (Medical) associated with Gepotidacin

01 Nov 2025·DRUGS

Gepotidacin: First Approval

Review

Author: Keam, Susan J

Gepotidacin (BLUJEPA), a small molecule triazaacenaphthylene bacterial type II topoisomerase inhibitor (BTI) antibacterial, has been developed by GSK for the treatment of uncomplicated urinary tract infections (uUTIs) and uncomplicated urogenital gonorrhoea (uUGC). In March 2025, gepotidacin was approved for the treatment of uUTIs caused by susceptible isolates of Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii complex, Staphylococcus saprophyticus and Enterococcus faecalis in female adult and paediatric patients aged ≥ 12 years and weighing ≥ 40 kg in the USA. This article summarizes the milestones in the development of gepotidacin leading to this first approval for the treatment of bacterial uUTIs.

01 Oct 2025·ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

Efficacy and in vitro activity of gepotidacin against bacterial uropathogens, including subsets with molecularly characterized resistance mechanisms and genotypes/epidemiological clones, in females with uncomplicated urinary tract infections: results from two global, pivotal, phase 3 trials (EAGLE-2 and EAGLE-3)

Article

Author: Scangarella-Oman, Nicole E. ; Breton, John ; Butler, Deborah L. ; Kasapidis, Cara ; Brown, Derrek ; Sheets, Amanda J.

ABSTRACT:

Gepotidacin, a novel, bactericidal, first-in-class triazaacenaphthylene antibacterial, was noninferior to nitrofurantoin in two pivotal trials (EAGLE-2 and EAGLE-3) in females with uncomplicated urinary tract infections (uUTIs). Using pooled data, gepotidacin in vitro activity and clinical efficacy were evaluated for subsets of molecularly characterized isolates in the microbiological Intent-to-Treat population. The subsets of isolates were characterized based on phenotypic/MIC criteria; all microbiological failure isolates were also characterized. Of 1,159 Escherichia coli isolates , 30% harbored quinolone resistance-determining region (QRDR) mutations; most prevalent was gyrA S83L, D87N (27%). Extended-spectrum β-lactamases (ESBLs) were detected in 13% of E. coli isolates. For 114 Klebsiella pneumoniae isolates, 22% were plasmid-mediated quinolone resistance (PMQR) gene-positive, 11% had QRDR mutations, and 12% had ESBLs. Among 67 Proteus mirabilis isolates, 21% harbored QRDR mutations. Gepotidacin MIC 90 values ranged from 1 to 32 µg/mL against qualifying Enterobacterales uropathogens and genotypic subcategories, with no isolates considered resistant to gepotidacin. For all genotypic subcategories, gepotidacin MIC 90 values were similar (i.e., lower, equal to, or 1-dilution higher) compared with the overall species (4 µg/mL), with the exception of E. coli isolates with the PMQR qnrS1 gene (16 µg/mL); all were gepotidacin-susceptible. For the majority of uropathogens, including those with genotypes likely to cause resistance to standard uUTI therapies, success rates for gepotidacin were similar across genotypic subcategories for each species. These data show gepotidacin’s efficacy and in vitro activity against a wide range of uropathogen genotypes. Additionally, these pooled results provide a robust, contemporary data set and insight into current genotypic mechanisms of resistance.

CLINICAL TRIALS:

This study is registered with ClinicalTrials.gov as NCT04020341 and NCT04187144 .

01 Oct 2025·JOURNAL OF INFECTION AND CHEMOTHERAPY

Oral gepotidacin for the treatment of uncomplicated urinary tract infection in Japanese female patients: a randomized, active reference, double-blind, double-dummy, Phase 3 trial (EAGLE-J)

Article

Author: Konishi, Takatoshi ; Banerjee, Rudrani ; Kameoka, Hiroshi ; Nakamura, Kiyoshi ; Igarashi, Hiroshi ; Maenaka, Takao ; Mori, Masaru ; Manabe, Fumio ; Huang, Tingwen ; Kayama, Yoko ; Suyama, Kenichi ; Yamamoto, Shingo ; Takashima, Hideo ; Scangarella-Oman, Nicole E. ; Hayami, Yutaro ; Ramirez, Marcela ; Ura, Shintaro ; Sekiguchi, Yuki ; Ogishima, Tatsuya ; Nimura, Akinori ; Kawahara, Motoshi ; Mozzicato, Susan ; Kamei, Maiko ; Sagiyama, Kazuyuki ; Iwata, Shinji ; Fujii, Kenji ; Hayashi, Mototaka ; Umeyama, Tomokazu ; Kamijo, Toshiyuki ; Kusuyama, Hiroyuki ; Kayama, Shigenori ; Hashimoto, Jiro ; Tanahashi, Yoshikatsu ; Nanri, Masaharu ; Muromiya, Yasuto ; Sugimoto, Kenji

BACKGROUND:

Two global Phase 3 trials, EAGLE-2 and EAGLE-3, found gepotidacin non-inferior (and superior in EAGLE-3) to nitrofurantoin for the treatment of uUTI in female participants, with an acceptable safety profile; however, these studies did not include Japanese centers.

METHODS:

EAGLE-J (NCT05630833; jRCT2031220467) was a Phase 3, randomized, double-blind, active reference study evaluating the efficacy and safety of gepotidacin for the treatment of uUTI in Japan. Eligible participants were females aged ≥12 years with ≥2 uUTI symptoms and urinary nitrite or pyuria. Participants were randomly assigned (3:1) oral gepotidacin (1500 mg) or nitrofurantoin (100 mg) twice daily for 5 days. To bridge data, consistency of therapeutic response at test-of-cure (day 10-13) in the gepotidacin arm of EAGLE-J with EAGLE-2/EAGLE-3 was assessed in participants with qualifying nitrofurantoin-susceptible uropathogens (≥10⁵ colony-forming units/mL). Therapeutic success comprised clinical (symptom resolution) and microbiological success (eradication). Consistency was claimed if the therapeutic success rate in EAGLE-J was greater than the consistency threshold predicted from EAGLE-2/EAGLE-3.

FINDINGS:

Overall, the primary analysis included 108 participants (83 gepotidacin, 25 nitrofurantoin). At test-of-cure, gepotidacin therapeutic success was 83.1 % (69/83), exceeding the consistency threshold (48.2 %). Adverse events were mostly mild-to-moderate; common adverse events were diarrhea (gepotidacin: 60 %, 168/281; nitrofurantoin: 8 %, 7/93) and nausea (gepotidacin: 12 %, 35/281; nitrofurantoin: 2 %, 2/93). No fatalities occurred.

INTERPRETATION:

Gepotidacin therapeutic success at test-of-cure was consistent between EAGLE-J and EAGLE-2/-3. Gepotidacin has potential as a valuable oral treatment option for uUTI in Japan. No new safety signals were identified.

54

News (Medical) associated with Gepotidacin

28 Nov 2025

·www.pharmaceutical-technology.com

MHRA approves Roche Products’ inavolisib for breast cancer

Inavolisib is not appropriate for patients who have received certain other cancer treatments in the recent past. Credit: NMK-Studio/Shutterstock.com. The UK Medicines and Healthcare products Regulatory Agency (MHRA) has granted approval to Roche Products’ inavolisib (Itovebi) to treat adults with hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. The approval enables the use of inavolisib in patients whose cancer has recurred during or shortly after hormone therapy and has metastasised to other areas of the body. Inavolisib is indicated for those whose cancer shows specific genetic changes and is not appropriate for patients who have received certain other cancer treatments in the recent past. The approved formulation is a film-coated tablet to be taken orally. A comprehensive list of side effects will be published in the Summary of Product Characteristics (SmPC) and the Patient Information Leaflet (PIL) on the MHRA website shortly after approval. Common side effects include high blood sugar, inflammation of the mouth (stomatitis), anaemia, diarrhoea, tiredness, decreased appetite, nausea, headache, rash, weight loss, urinary tract infections and vomiting. GlobalData Strategic Intelligence US Tariffs are shifting - will you react or anticipate? Don’t let policy changes catch you off guard. Stay proactive with real-time data and expert analysis. By GlobalData Learn more about Strategic Intelligence Patients experiencing potential side effects are advised to consult a doctor, nurse or pharmacist. Inavolisib is subject to additional monitoring, allowing rapid identification of new safety information. Reporting suspected adverse reactions post-authorisation is essential for ongoing evaluation of the medicine’s benefit/risk balance. MHRA healthcare quality and access interim executive director Julian Beach stated: “The approval of inavolisib provides a new targeted treatment for people with advanced breast cancer that has returned or spread after hormone therapy. “Inavolisib can help delay the progression of the disease, giving patients more time with effective treatment. As with all licensed medicines, we will continue to monitor its safety and effectiveness closely as it becomes more widely used.” In August 2025, MHRA granted approval to GSK’s oral antibiotic pill, Blujepa (gepotidacin), for uncomplicated urinary tract infections in females aged 12 and above with a minimum body weight of 40kg. Pharmaceutical Technology Excellence Awards - The Benefits of Entering Gain the recognition you deserve! The Pharmaceutical Technology Excellence Awards celebrate innovation, leadership, and impact. By entering, you showcase your achievements, elevate your industry profile, and position yourself among top leaders driving pharmaceutical advancements. Don’t miss your chance to stand out—submit your entry today! Nominate Now

Drug Approval

21 Oct 2025

·endpoints.news

GSK, Spero reveal full Phase 3 data for oral antibiotic, set for end-of-year filing

GSK and Spero Therapeutics are taking their oral antibiotic to the FDA after reporting the full Phase 3 non-inferiority data. The companies said Monday that tebipenem HBr performed no worse than an approved IV antibiotic regimen for complicated urinary tract infections (cUTIs), and all side effects were mild or moderate. Looking at overall responses, patients taking tebipenem HBr saw a 58.5% success rate compared to 60.2% for the IV regimen, which is known as imipenem-cilastatin. Additionally, 93.5% of patients treated with tebipenem HBr did not have any symptoms after treatment, compared to 95.2% in the control group. With the data in hand, Spero said GSK is ready to submit the data package to the FDA by the end of the year — as previously announced. Its share price $SPRO was up about 4% on Tuesday morning. GSK and Spero stopped the trial in May due to efficacy, giving Spero a lifeline and lifting it out of penny-stock status. Spero developed the antibiotic and tried getting it approved by itself, but the agency rejected the drug in 2022. At the time, FDA officials felt the data package was not sufficient to support approval, according to feedback they provided to Spero . A few months later, GSK signed a licensing deal with Spero that’s worth $66 million upfront plus milestones totaling $525 million. The “delivery” of the Phase 3 data entitles Spero to a $150 million milestone. GSK is handling the FDA application. Despite the emergence of drug-resistant “superbug” bacteria, antibiotics are not traditionally a popular investment. But GSK has found some recent success. In March, the FDA approved another GSK antibiotic program for uncomplicated UTIs, and the company is also testing that drug — branded as Blujepa — as a treatment for gonorrhea . It’s also preparing to pitch tebipenem HBr as a tool to keep patients from being admitted to the hospital.

Phase 3License out/inClinical Result

03 Sep 2025

·pmlive.com

UK’s first new type of antibiotic for UTIs in nearly 30 years approved by MHRA

Gepotidacin (Blujepa) has been approved by the Medicines and Healthcare products Regulatory Agency (MHRA) for use by women and girls from 12 years of age, with a weight of at least 40kg. The new antibiotic is an oral pill that can be used to treat uncomplicated urinary tract infections (UTIs). It is effective against many drug-resistant infections, including E. coli, using an active ingredient that targets and blocks two enzymes that bacteria need to replicate and multiply. This type of UTI affects around 50% of women in the UK and is the most common bacterial infection in women. With drug-resistant bacteria increasing, new treatment options are critical in preventing treatment failure and complications, including sepsis or permanent kidney damage. Julian Beach, MHRA Interim Executive Director, Healthcare Quality and Access, said: “As the first new type of oral antibiotic to treat uncomplicated UTIs to be approved in nearly three decades, gepotidacin provides a new treatment option for women facing urinary tract infections that can severely impact daily life. “The antibiotic’s targeted mechanism of action makes it more difficult for bacteria to develop treatment resistance – a crucial factor as drug-resistant bacteria are increasingly on the rise globally.” Results from two multicentre, randomised, active-controlled phase 3 trials were used as evidence to support the new drug approval. In the trials, 1,572 participants were given gepotidacin and 1,564 received nitrofurantoin, the current treatment for uncomplicated UTIs. In both trials, gepotidacin was shown to be at least as effective as nitrofurantoin, with consistent results across patient groups, including those with drug-resistant bacteria and recurrent infections.

Phase 3Clinical ResultDrug ApprovalQualified Infectious Disease Product

100 Deals associated with Gepotidacin

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External Link

KEGG	Wiki	ATC	Drug Bank
D10878	Gepotidacin	-	DB12134

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Bacterial Infections	United States	GlaxoSmithKline LLC	25 Mar 2025
Urinary Tract Infections	United States	GlaxoSmithKline LLC	25 Mar 2025

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Gonococcal urethritis	Phase 3	United States	GSK Plc	21 Oct 2019
Gonococcal urethritis	Phase 3	Australia	GSK Plc	21 Oct 2019
Gonococcal urethritis	Phase 3	Germany	GSK Plc	21 Oct 2019
Gonococcal urethritis	Phase 3	Mexico	GSK Plc	21 Oct 2019
Gonococcal urethritis	Phase 3	Spain	GSK Plc	21 Oct 2019
Gonococcal urethritis	Phase 3	United Kingdom	GSK Plc	21 Oct 2019
Acute cystitis	Phase 3	United States	GSK Plc	17 Oct 2019
Acute cystitis	Phase 3	Bulgaria	GSK Plc	17 Oct 2019
Acute cystitis	Phase 3	Czechia	GSK Plc	17 Oct 2019
Acute cystitis	Phase 3	Germany	GSK Plc	17 Oct 2019

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04187144 \| NCT04020341 (FDA_CDER) Manual	Phase 3	Bacterial Infections \| Urinary Tract Infections	-	BLUJEPA (Trial 1)	ppldesymcx(fjusebkdwt) = xumtzgynby thaprxsebi (yxsoliofar ) View more	Positive	25 Mar 2025
				Nitrofurantoin (Trial 1)	ppldesymcx(fjusebkdwt) = slcotfhubk thaprxsebi (yxsoliofar ) View more
NCT05630833 (EAGLE-J, CTgov)	Phase 3	Urinary Tract Infections \| Acute cystitis \| Pyuria	380	Gepotidacin (Gepotidacin)	pfcbxlqhdx = uhidzfztdq dbhgegavnn (hctyopudyr, oiembtmkko - xmfxojzmrg) View more	-	17 Mar 2025
				Nitrofurantoin (Nitrofurantoin)	drjelmmers = cuvjohepyi zzmvmnpqdk (flzsarehtf, xieoibkewz - pkeoembaki) View more
NCT04010539 (EAGLE-1, CTgov)	Phase 3	Gonococcal urethritis	628	Gepotidacin (Gepotidacin)	qtfdcvkeqv = mdwpwzwszy lpterbexjb (ckxbibmzap, dbldzkiuov - aslnvdwoff) View more	-	30 May 2024
				Azithromycin+Ceftriaxone (Ceftriaxone Plus Azithromycin)	qtfdcvkeqv = trtlhyyuio lpterbexjb (ckxbibmzap, bxzerxphof - okzdkummte) View more
NCT04010539 (EAGLE-1, NEWS) Manual	Phase 3	Gonorrhea	600	gepotidacin (oral, two doses of 3,000mg)	ryhxfmkjoh(dwfwjyrvrd) = rgjcizcron rzxkcrsveu (wjuhjnbcnc )	Positive	18 Apr 2024
				intramuscular (IM) ceftriaxone (500mg) plus oral azithromycin (1,000mg) combined therapy	ryhxfmkjoh(dwfwjyrvrd) = fjhaddrqbj rzxkcrsveu (wjuhjnbcnc )
NCT04010539 (EAGLE-1, NEWS) Manual	Phase 3	Gonorrhea	-	Gepotidacin	cctabjoeia(qockqvbdsk) = proving to be as effective as an existing treatment for the infection. uvetqdxngo (pwmqgmjvyt ) Met	Non-inferior	26 Feb 2024
				Ceftriaxone+Azithromycin
NCT04187144 (EAGLE-3, CTgov)	Phase 3	Urinary Tract Infections \| Acute cystitis \| Pyuria	1,606	Placebo matching nitrofurantoin+Gepotidacin (Gepotidacin)	paleqabzlk = upbwziqlxg visgvpgkwg (mxccyrwmfo, raldauqhtm - uzvhrnxcyx) View more	-	18 Jul 2023
				Placebo matching gepotidacin+Nitrofurantoin (Nitrofurantoin)	paleqabzlk = apdvywdtze visgvpgkwg (mxccyrwmfo, agggqopayb - ocahlixcns) View more
NCT04020341 (CTgov)	Phase 3	Urinary Tract Infections \| Acute cystitis \| Pyuria	1,531	Placebo matching nitrofurantoin+Gepotidacin (Gepotidacin)	hfcqlvmcif = kvsssoueny ydtqvnknuz (ctvtwmrezk, lsblldkjgq - sflavuwoax) View more	-	22 Jun 2023
				Placebo matching gepotidacin+Nitrofurantoin (Nitrofurantoin)	hfcqlvmcif = bcjunmuilh ydtqvnknuz (ctvtwmrezk, pohmkdeobe - ymjladwyzc) View more
NCT02294682 (Pubmed \| Sex Transm Infect)	Phase 3	Gonorrhea	-	Gepotidacin 3000 mg	qbzqrqujzt(gmadhtjybf) = njjqwvhyea cezhlgdglm (nhvdqgaxrz )	-	21 Nov 2022
NCT04187144 (EAGLE-3, Corporate Publications) Manual	Phase 3	Urinary Tract Infections	2,500	Gepotidacin	imewsugtun(csdavlidjh) = met the primary efficacy endpoint ruvyockckb (wqzzozfsie ) Met	Non-inferior	03 Nov 2022
				Nitrofurantoin
NCT04079790 (CTgov)	Phase 1	Bacterial Infections	34	Gepotidacin (Part 1: Gepotidacin 1500 mg)	wmmydmlvre(pqvjphbrgb) = curtisjmxu ycqymmpefr (eieyuoscis, 17.6) View more	-	04 Sep 2020
				Gepotidacin (Part 1: Gepotidacin 3000 mg 12 Hour Interval)	jfmpvvgghv(ylpyskxgsl) = lyiohoscpq enlsdyauxw (adxcdtixyq, 22.6) View more