REG - GSK PLC - GSK stops Phase 3 trial on cUTIs for efficacy

GSKAnnouncement

28/05/2025 12:00

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RNS Number : 3973K  GSK PLC  28 May 2025

Issued: 28 May 2025, London UK

 

PIVOT-PO phase III study for tebipenem HBr stopped early for efficacy
following review by Independent Data Monitoring Committee

 

·   If approved, tebipenem HBr could be the first oral carbapenem
antibiotic for US patients with complicated urinary tract infections (cUTIs)

·   Data to be part of a planned US FDA filing in H2 2025

·   An estimated 2.9 million cases of cUTIs are treated annually in the
US 1  (#_edn1) with many cases requiring hospitalisation, contributing to over
$6 billion per year in healthcare costs 2  (#_edn2)

·   GSK's second anti-infective programme stopped early for efficacy in
Phase III after EAGLE 2 and 3 for gepotidacin 3  (#_edn3)

 

 

 

GSK plc (LSE/NYSE: GSK) and Spero Therapeutics today announced that the
pivotal phase III PIVOT-PO trial evaluating tebipenem HBr, an investigational
oral treatment for complicated urinary tract infections (cUTIs), including
pyelonephritis, will stop early for efficacy (NCT06059846). The decision
follows a recommendation from an Independent Data Monitoring Committee (IDMC),
based on a planned interim analysis of data from 1,690 patients enrolled in
the study. If approved, tebipenem HBr would be the first oral carbapenem
antibiotic for patients in the US who suffer from cUTIs, adding to GSK's
innovative anti-infectives portfolio and helping address the challenges of
antimicrobial resistance (AMR).

 

The trial met the primary endpoint of non-inferiority of tebipenem HBr
compared to intravenous imipenem-cilastatin in hospitalised adult patients
with cUTI, including pyelonephritis, on overall response (composite of
clinical cure plus microbiological eradication) at the test-of-cure visit. The
IDMC review did not identify any new safety concerns beyond what has been
reported in other studies with tebipenem, with diarrhea and headache as the
two most reported adverse events. GSK plans to work with US regulatory
authorities to include the data as part of a filing in H2 2025. Full results
will be submitted for presentation at an upcoming scientific congress and for
publication in a peer-reviewed journal.

 

Tony Wood, Chief Scientific Officer, GSK, said: "Complicated UTIs can have a
profound impact on patients and carry a high risk of clinical complications,
including sepsis and septic shock. 4  (#_edn4) (, 5  (#_edn5) , 6  (#_edn6) )
Currently many need hospital-based intravenous treatment due to limited oral
options for drug-resistant infections, contributing to over $6 billion per
year in US healthcare costs(2). These positive results add to our growing
anti-infectives portfolio and reinforce the potential of tebipenem HBr as an
effective oral alternative taken at home".

 

An estimated 2.9 million cases of cUTIs are treated annually in the US
alone.(1) These infections are often caused by multidrug-resistant
pathogens(1) and carry increased risk of morbidity and mortality.(4)(,)(7)
Current standard of care includes carbapenem antibiotics, especially in case
of sepsis and allergies or resistance to other antibiotics, but they are only
available for IV administration. This results in significant emergency
department visits and hospitalisations.(6, 7  (#_edn7) , 8  (#_edn8) )

 

Esther Rajavelu, Chief Executive Officer, Spero Therapeutics, said: "We're
proud of today's positive result for patients diagnosed with cUTI,
including pyelonephritis, where oral treatments are much needed. We look
forward to working with GSK on next steps for tebipenem HBr, and would like to
thank the patients, investigators, and other clinical staff who have
participated in PIVOT-PO trial to reach this advanced stage."

 

The development of tebipenem HBr is supported in part with federal funds from
the U.S. Department of Health and Human Services; Administration for Strategic
Preparedness and Response; Biomedical Advanced Research and Development
Authority (BARDA), under contract number HHSO100201800015C. It is GSK's
second anti-infective programme to be stopped early for efficacy in Phase III,
following the EAGLE 2 and EAGLE 3 trials for gepotidacin in 2022.(3)

 

About tebipenem HBr

Tebipenem pivoxil hydrobromide (HBr) is a late-stage development asset
developed in collaboration with Spero Therapeutics. Tebipenem HBr is being
developed to treat cUTIs, including pyelonephritis. In September 2022, GSK
entered into an exclusive license agreement with Spero Therapeutics for the
development and commercialisation of tebipenem HBr in all markets, except
certain Asian territories. Under this agreement GSK has sub-licensed back to
Spero Therapeutics the rights and responsibility to conduct certain
development work including the PIVOT-PO Phase III study, after which
sponsorship of the new drug application (NDA) will be transferred to GSK from
Spero Therapeutics. Tebipenem HBr has received Qualified Infectious Disease
Product (QIDP) and Fast Track designations from the US FDA.

 

About the PIVOT-PO trial

PIVOT-PO is a global, randomised, double-blind, pivotal Phase III clinical
trial of oral tebipenem pivoxil HBr compared to IV imipenem, in hospitalised
adult patients with cUTI including pyelonephritis. Patients were randomised
1:1 to receive tebipenem pivoxil (600 mg) orally every six hours, or
imipenem-cilastin (500 mg) IV every six hours, for a total of seven to ten
days. Matching placebos are used to maintain blinding. The primary efficacy
endpoint is overall response (composite of clinical cure plus microbiological
eradication) at the test-of-cure visit. The primary analysis for the trial is
an assessment of non-inferiority in the primary analysis population. The trial
enrolled a total of 1690 patients, with randomisation stratified by age,
baseline diagnosis (cUTI or pyelonephritis), and the presence or absence of
urinary tract instrumentation. For further details on the trial, refer to
clinicaltrials.gov identifier NCT06059846.

 

About complicated urinary tract infections (cUTIs)

cUTIs are broadly described as any UTI that carries an increased risk of
morbidity and mortality.(4) Definitions of cUTIs are not currently uniform
among international societies and regulatory agencies. 9  (#_edn9) cUTIs
encompass a heterogeneous patient population due to the wide range of host
factors, comorbidities and urological abnormalities associated with
cUTIs.(4,9) Risk factors for cUTI include indwelling catheters, ureteric
stents, neurogenic bladder, obstructive uropathy, urinary retention, urinary
diversion, kidney stones, diabetes mellitus, immune deficiency, urinary tract
modification, and UTIs in renal transplant patients. 10  (#_edn10)

 

GSK in infectious diseases

GSK has pioneered innovation in infectious diseases for over 70 years, and the
Company's pipeline of medicines and vaccines is one of the largest and most
diverse in the industry, with a goal of developing preventive and therapeutic
treatments for multiple disease areas or diseases with high unmet needs
globally. Our expertise and capabilities in infectious disease strongly
position us to help prevent disease and mitigate the challenge of
antimicrobial resistance (AMR).

 

About Spero Therapeutics

Spero Therapeutics, headquartered in Cambridge, Massachusetts, is a
clinical-stage biopharmaceutical company focused on identifying and developing
novel treatments for rare diseases and multi-drug resistant (MDR) bacterial
infections with high unmet need. For more information, visit
www.sperotherapeutics.com (http://www.sperotherapeutics.com)

 

About GSK

GSK is a global biopharma company with a purpose to unite science, technology,
and talent to get ahead of disease together. Find out more at gsk.com.

 

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Cautionary statement regarding forward-looking statements

GSK cautions investors that any forward-looking statements or projections made
by GSK, including those made in this announcement, are subject to risks and
uncertainties that may cause actual results to differ materially from those
projected. Such factors include, but are not limited to, those described in
the "Risk Factors" section in GSK's Annual Report on Form 20-F for 2024, and
GSK's Q1 Results for 2025.

 

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References

 1  (#_ednref1) Carreno JJ, et al. Longitudinal, Nationwide, Cohort Study to
Assess Incidence, Outcomes, and Costs Associated With Complicated Urinary
Tract Infection. Open Forum Infect Dis. 2019;6:ofz446.

 2  (#_ednref2) Lodise TP, et al. Hospital admission patterns of adult
patients with complicated urinary tract infections who present to the hospital
by disease acuity and comorbid conditions: How many admissions are potentially
avoidable? Am J Infect Control. 2021;49(12):1528-1534.

 3  (#_ednref3) GSK press release, 3 November 2022 - available at:
https://www.gsk.com/en-gb/media/press-releases/gsk-announces-phase-iii-trials-for-gepotidacin/
(https://www.gsk.com/en-gb/media/press-releases/gsk-announces-phase-iii-trials-for-gepotidacin/)

 4  (#_ednref4) Sabih A, Leslie SW. Complicated urinary tract infections.
StatPearls. 2023. StatPearls Publishing: Treasure Island, FL, USA.

 5  (#_ednref5) Zilberberg MD, et al. Descriptive Epidemiology and Outcomes of
Hospitalisations With Complicated Urinary Tract Infections in the United
States, 2018. Open Forum Infect Dis. 2022;9:ofab591.

 6  (#_ednref6) Li HK, et al. An Unsupported Preference for Intravenous
Antibiotics. PLoS Med. 2015;12:e1001825.

 7  (#_ednref7) Vallejo-Torres L, et al. Cost of hospitalised patients due to
complicated urinary tract infections: a retrospective observational study in
countries with high prevalence of multidrug-resistant Gram-negative bacteria:
the COMBACTE-MAGNET, RESCUING study. BMJ Open. 2018;8:e020251.

 8  (#_ednref8) Lodise TP, et al. Retrospective Cohort Study of the 12-Month
Epidemiology, Treatment Patterns, Outcomes, and Health Care Costs Among Adult
Patients With Complicated Urinary Tract Infections. Open Forum Infect Dis.
2022;9:ofac307.

 9  (#_ednref9) Marantidis J, Sussman RD. Unmet Needs in Complicated Urinary
Tract Infections: Challenges, Recommendations, and Emerging Treatment
Pathways. Infect Drug Resist. 2023:16:1391-1405.

 10  (#_ednref10) Gomila A, et al. Predictive factors for multidrug-resistant
gram-negative bacteria among hospitalised patients with complicated urinary
tract infections. Antimicrob Resist Infect Control. 2018;7:111.

 

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