REG - GSK PLC - GSK share positive Ph3 data on tebipenem HBr

GSKAnnouncement

21/10/2025 07:00

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RNS Number : 0925E  GSK PLC  21 October 2025

Issued: 21 October 2025, London UK

 

Positive PIVOT-PO phase III data show tebipenem HBr's potential as the first
oral carbapenem antibiotic for patients with complicated urinary tract
infections (cUTIs)

 

·   Data presented at IDWeek 2025 after study stopped early for efficacy

· Primary endpoint met, demonstrating non-inferiority of oral tebipenem HBr
compared to intravenous treatment(1)

·   A new oral option may reduce the need for cUTI treatment in hospital
setting

·   Data will be shared with regulatory authorities to support regulatory
filings

 

 

 

GSK plc (LSE/NYSE: GSK) and Spero Therapeutics (Nasdaq: SPRO) today announced
full results of the positive pivotal phase III PIVOT-PO trial evaluating
tebipenem HBr, an investigational oral treatment for complicated urinary tract
infections (cUTIs), including pyelonephritis (NCT06059846). These results were
presented on 20 October 2025 in a late-breaking oral abstract session at ID
Week 2025 in Atlanta, USA.

 

Complicated UTIs represent an important health issue, with an estimated 2.9
million cases of cUTIs treated annually in the US alone.(2) These infections
are often caused by multidrug-resistant pathogens(3) and carry serious risks
including organ failure, sepsis, and even death.(3-5) They also result in
significant emergency department visits and hospitalisations, contributing to
over $6 billion per year in healthcare costs.(6) Current standard of care
includes carbapenem antibiotics in cases of sepsis or resistance to other
antibiotics but they are only available for intravenous administration
typically occurring in hospital setting.(7,8)

 

The trial, which was stopped early for efficacy in May, demonstrated
non-inferiority of tebipenem HBr compared to intravenous imipenem-cilastatin
in hospitalised patients with cUTI, including pyelonephritis, based on the
overall response (composite of clinical cure plus microbiological eradication
of the bacteria causing the infection) at the test of cure visit. Tebipenem
HBr (oral, 600 mg) achieved a 58.5% overall success rate (261/446
participants) compared to 60.2% overall success rate (291/483 participants)
for imipenem-cilastatin (intravenous, 500 mg) (adjusted treatment difference:
−1.3%; 95% CI: −7.5%, 4.8%). The safety profile of tebipenem HBr was
generally similar to that of imipenem-cilastatin and other carbapenem
antibiotics. The most frequently reported adverse events (in ≥3% of patients
who received tebipenem HBr) were diarrhea and headache; these events were all
mild or moderate and non-serious.

 

Tony Wood, Chief Scientific Officer, GSK, said: "Complicated UTIs can have
serious consequences for patients, including organ failure and sepsis, and
oral options for drug-resistant infections are limited. These ground-breaking
data show for the first time that cUTIs, including pyelonephritis, can be
treated with an oral carbapenem antibiotic as effectively as with an
intravenous one. We have a long-standing commitment to delivering novel
anti-infectives and are delighted to offer the potential of tebipenem HBr as
an effective oral alternative that could be taken at home".

 

Esther Rajavelu, Chief Executive Officer, Spero Therapeutics, said: "These
data presented at IDWeek represent the culmination of years of dedicated work
by our team in close collaboration with GSK. We are deeply grateful to the
physicians, researchers, support staff, and, most importantly, to the patients
who made this study, and the ones before it, possible. Along with GSK, we are
now focused on advancing tebipenem HBr toward FDA submission and bringing this
important therapy to patients in need."

 

Dr George Sakoulas, Adjunct Professor Department of Pediatrics, UCSD School of
Medicine and Chief Infectious Diseases Sharp Rees Stealy Medical Group,
commented: "Increasing antibiotic resistance among community-acquired bacteria
that cause cUTIs is greatly amplifying the burden of treatment for patients,
clinicians, and payers. The therapeutic flexibility of a new oral antibiotic
may reduce the need for intravenous antibiotics to treat cUTI, providing
benefit to patients and improving treatment options."

 

Secondary endpoints also show:

·      Clinical cure (i.e. absence of symptoms) rates at test of cure
visit were 93.5% in the tebipenem HBr group (417/446) compared to 95.2% in the
imipenem-cilastatin group (460/483) with adjusted treatment difference:
−1.6% (95% CI: −4.7%, 1.4%)

·      Microbiological response rates at test of cure visit were 60.3%
in the tebipenem HBr group (269/446) compared to 61.3% in the
imipenem-cilastatin group (296/483) with adjusted treatment difference:
−0.8% (95% CI: −6.9%, 5.3%)

·      Overall, clinical and microbiological response rates at test of
cure in participants with infections caused by antimicrobial-resistant
Enterobacterales were consistent with the respective response rates in the
primary analysis population.

 

GSK plans to work with US regulatory authorities to include the data as part
of a filing in Q4 2025. If approved, tebipenem HBr would be the first oral
carbapenem antibiotic in the US for patients who suffer from cUTIs, adding to
GSK's growing anti-infectives portfolio and helping address the challenges of
antimicrobial resistance (AMR).

 

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.

 

About tebipenem HBr

Tebipenem pivoxil as hydrobromide salt (Tebipenem 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 was a global, randomised, double-blind, pivotal, non-inferiority (NI
margin: -10%) Phase 3 clinical trial of oral tebipenem HBr compared to IV
imipenem-cilastatin, 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-cilastatin (500 mg) IV every six
hours, for a total of seven to ten days. Matching placebos were used to
maintain blinding. The primary efficacy endpoint was overall response
(composite of clinical cure plus microbiological eradication) at the
test-of-cure visit (about 17 days from first dose administration of study
drug) in patients with qualifying pathogens susceptible to imipenem. The trial
enrolled a total of 1,690 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.(3) Definitions of cUTIs are not currently uniform
among international societies and regulatory agencies.(5, 9) cUTIs encompass a
heterogeneous patient population due to the wide range of host factors,
comorbidities and urological abnormalities associated with cUTIs.(5, 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.(3, 10-13)

 

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 and treat disease, and potentially 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 Q2 Results for 2025.

 

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References

 

1.  Hong D. et al, Oral Tebipenem Pivoxil Hydrobromide vs Intravenous
Imipenem-Cilastatin in Patients with Complicated Urinary Tract Infections or
Acute Pyelonephritis: Efficacy and Safety Results from the Phase 3 PIVOT-PO
study, Oral presentation at ID Week 2025, 20 October 2025. .

2.  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.

3.  Sabih A, Leslie SW. Complicated urinary tract infections. In: StatPearls.
2023. StatPearls Publishing: Treasure Island, FL, USA.

4.  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.

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

6.  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.

7.  Cotroneo, N., et al. In Vitro and In Vivo Characterization of Tebipenem,
an Oral Carbapenem. Antimicrobial agents and chemotherapy. 2020. 64(8),
e02240-19.

8.  Maeda M, et al. Efficacy of carbapenems versus alternative antimicrobials
for treating complicated urinary tract infections caused by
antimicrobial-resistant Gram-negative bacteria: protocol for a systematic
review and meta-analysis. BMJ Open. 2023 Apr 21;13(4):e069166.

9.  Fernandez MM, et al. Poster presented at ESCMID Global, 27-30 April 2024,
Barcelona, Spain. Poster P1023.

10.  Bonkat G, et al. Keep it Simple: A Proposal for a New Definition of
Uncomplicated and Complicated Urinary Tract Infections from the EAU Urological
Infections Guidelines Panel. Eur Urol. 2024;86(3):195-197.

11.  Wagenlehner FME, et al. Epidemiology, definition and treatment of
complicated urinary tract infections. Nat Rev Urol. 2020;17(10):586-600.

12.  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.

13.  Altunal N, et al. Ureteral stent infections: a prospective study. Braz J
Infect Dis. 2017;21(3):361-364.

 

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