UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
Form 6-K
REPORT OF FOREIGN PRIVATE ISSUER PURSUANT TO RULE 13a-16 OR
15d-16
UNDER THE SECURITIES EXCHANGE ACT OF 1934
For the
month of April 2023
Commission
File Number 001-15170
GSK plc
(Translation
of registrant's name into English)
980 Great West Road, Brentford, Middlesex, TW8 9GS
(Address
of principal executive office)
Indicate
by check mark whether the registrant files or will file annual
reports under cover of Form 20-F or Form 40-F.
Form
20-F . . . .X. . . . Form 40-F . . . . . . . .
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by check mark if the registrant is submitting the Form 6-K in paper
as permitted by Regulation S-T Rule 101(b)(1): ____
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Issued:
15 April 2023, London UK
Gepotidacin's positive phase III data shows potential to be the
first in a new class of oral antibiotics for uncomplicated urinary
tract infections in over 20 years
● Gepotidacin is a late-stage antibiotic in
development in GSK's growing infectious diseases
portfolio
● EAGLE-2 and EAGLE-3 phase III trials met primary
endpoint of non-inferiority to nitrofurantoin; EAGLE-3 demonstrated
statistical superiority
● US FDA submission is planned for Q2
2023
GSK plc
(LSE/NYSE: GSK) presented positive results from the pivotal EAGLE-2
and EAGLE-3 phase III trials for gepotidacin, an investigational,
first-in-class oral antibiotic with a novel mechanism of action for
uncomplicated urinary tract infections (uUTI) in female adults and
adolescents. The data were disclosed today in an oral presentation
at the European Congress of Clinical Microbiology and Infectious
Diseases (ECCMID) in Copenhagen, Denmark.
These
positive data highlight GSK's world-leading infectious diseases
portfolio, which represents about two-thirds of the Company's
pipeline. In addition, they reinforce GSK's commitment to
developing new antibiotics in high unmet medical need areas, such
as uUTI. Today's presentation follows the decision to stop the
EAGLE-2 and EAGLE-3 pivotal trials early for efficacy following a
recommendation made by the Independent Data Monitoring Committee in
November 2022. The full results will be submitted for publication
in a peer-reviewed scientific journal later this year.
Over
half of all women are affected by uUTIs in their
lifetime[1], with more than a
quarter suffering from recurrent disease[2],[3],[4] , which can
cause significant patient burden, including discomfort and
restriction of daily activities. The number of uUTIs caused by
resistant bacteria is increasing, which can result in higher
treatment failure rates.[5]
Chris Corsico, SVP Development, GSK, said: "Despite uncomplicated urinary tract infections
being one of the most common infections in women and mounting
concern over rising resistance rates to existing treatments, there
has been no new class of antibiotics for over 20 years. We believe
that gepotidacin, if approved, will offer a much-needed additional
oral treatment option for patients at risk of treatment failure
associated with resistance or recurrence of uUTI. We are committed
to working with global regulators to bring this new antibiotic to
patients as quickly as possible."
In the
EAGLE-2 and EAGLE-3 phase III trials, gepotidacin demonstrated
non-inferiority to nitrofurantoin, an existing first-line treatment
for uUTI, in patients with a confirmed uUTI and a uropathogen
susceptible to nitrofurantoin. Additionally, in the EAGLE-3 phase
III trial, gepotidacin demonstrated statistically significant
superiority versus nitrofurantoin. These results are based on a
primary efficacy endpoint of therapeutic success, an endpoint
comprised of combined clinical resolution and microbiological
eradication of bacteria at the Test-of-Cure (ToC) visit 10-13 days
after initiation of treatment.
In the
EAGLE-2 phase III trial, gepotidacin demonstrated therapeutic
success in 50.6% of patients compared to 47% for nitrofurantoin. In
the EAGLE-3 phase III trial, gepotidacin demonstrated therapeutic
success in 58.5% of patients compared to 43.6% for nitrofurantoin.
Across both trials, it was noted that 94% of patients treated with
gepotidacin did not receive an additional antibiotic for uUTI
during trial participation through the follow-up visit on day 28.
The safety and tolerability profile of gepotidacin in the EAGLE-2
and EAGLE-3 phase III trials was consistent with previous trials of
gepotidacin.
Gepotidacin
also demonstrated consistent efficacy (therapeutic success)
compared to nitrofurantoin in key subgroups, including patients
with Escherichia
coli pathogens resistant to other antibiotics, those
with a history of recurrence and those over 50 years old. These
subgroups are at higher risk of treatment failure.[6],[7]
The
table below summarises the key efficacy data for phase III trials
at the ToC visit:
|
EAGLE-2
|
EAGLE-3
|
Gepotidacin 1,500mg BID (n=320)
|
Nitrofurantoin 100mg BID (n=287)
|
Treatment Differencei (95%
CI)
|
Gepotidacin 1,500mg BID (n=277)
|
Nitrofurantoin 100mg BID (n=264)
|
Treatment Differencei
(95% CI)
|
Therapeutic
successii
|
162 (50.6%)
|
135 (47.0%)
|
4.3%
(-3.6%,
12.1%)
|
162 (58.5%)
|
115 (43.6%)
|
14.6%
(6.4%,
22.8%)
|
Clinical
successiii
|
210 (65.6%)
|
187 (65.2%)
|
1.2%
(-6.3%,
8.7%)
|
188 (67.9%)
|
167 (63.3%)
|
4.4%
(-3.5%,
12.3%)
|
Microbiological
successiv
|
232 (72.5%)
|
194 (67.6%)
|
5.2%
(-2.1%,
12.5%)
|
200 (72.2%)
|
151 (57.2%)
|
15.0%
(7.2%,
22.9%)
|
Both
trials were stopped for non-inferiority based on pre-defined
non-inferiority success boundaries. In addition, the EAGLE-3 phase
III trial met the pre-defined boundary for
superiority.
i Difference: gepotidacin - nitrofurantoin.
Micro-ITT NTF-S (IA set), the microbiological intent-to-treat
nitrofurantoin- susceptible interim analysis set
population
ii Composite endpoint of clinical and
microbiological success
iii Clinical
success at Test-Of-Cure (TOC) = symptom
resolution
iv Eradication
of qualifying uropathogen to <103 CFU/mL
Prof. Dr Florian Martin Erich Wagenlehner, Principal Investigator
for the EAGLE-2 phase III trial, said: "These results are a significant step forward in
an area that has seen very little innovation for decades.
Gepotidacin is the first antibiotic to meet contemporary regulatory
criteria, which set a high threshold for the efficacy of treatments
in uncomplicated urinary tract infections. Gepotidacin has the
potential to offer healthcare professionals another oral option to
treat this common community infection."
The
most commonly reported adverse events (AEs) in gepotidacin subjects
were gastrointestinal (GI). Diarrhoea was the most common (16% of
subjects), followed by nausea (9%). Of the subjects who reported GI
AEs in the gepotidacin arm, the maximum severity of most subjects
were mild (69% Grade 1) and moderate (28% Grade 2). Grade 3 GI
events were 3% of the total GI events and occurred in <1% of
subjects. There was one drug-related serious adverse event in each
treatment arm (gepotidacin and nitrofurantoin) across the two
trials.
The
development of gepotidacin has been funded in whole or in part with
U.S. federal funds from the U.S. Department of Health and Human
Services, Administration for Strategic Preparedness and Response,
Biomedical Advanced Research and Development Authority, under Other
Transaction Agreement number HHSO100201300011C and with federal
funds awarded by the Defense Threat Reduction Agency under
agreement number HDTRA1-07-9-0002.
About the EAGLE (Efficacy of Antibacterial Gepotidacin Evaluated)
phase III programme
The
phase III clinical programme for gepotidacin in adults and
adolescents comprises three trials:
The
EAGLE-2 and EAGLE-3 phase III trials were near-identical global,
randomised, parallel-group, double-blind, non-inferiority (10%
margin) trials comparing the efficacy and safety of oral
gepotidacin to nitrofurantoin for the treatment of uUTI. A total of
3,136 patients were enrolled across both trials.
EAGLE-2
(non-inferiority uUTI trial) compared the efficacy and safety of
gepotidacin (1,500mg administered orally twice daily for five days)
to nitrofurantoin (100mg administered orally twice daily for five
days). The trial duration for participants was approximately 28
days. The primary endpoint was the combined clinical and
microbiological response at the ToC visit (days 10-13) in patients
with qualifying uropathogens susceptible to
nitrofurantoin.
EAGLE-3
(non-inferiority uUTI trial) compared the efficacy and safety of
gepotidacin (1,500mg administered orally twice daily for five days)
to nitrofurantoin (100mg administered orally twice daily for five
days). The trial duration for participants was approximately 28
days. The primary endpoint was the combined clinical and
microbiological response at the ToC visit (days 10-13) in patients
with qualifying uropathogens susceptible to
nitrofurantoin.
EAGLE-1
(non-inferiority urogenital gonorrhoea trial) compares the efficacy
and safety of gepotidacin to ceftriaxone plus azithromycin in
approximately 600 patients with uncomplicated urogenital gonorrhoea
caused by Neisseria
gonorrhoeae. The EAGLE-1 trial is investigating gepotidacin
for the treatment of uncomplicated urogenital gonorrhoea and is
ongoing, with a data read out anticipated in the second half of
2023.
About gepotidacin
Gepotidacin,
discovered by GSK scientists, is an investigational bactericidal,
first-in-class triazaacenaphthylene antibiotic that inhibits
bacterial DNA replication by a novel mechanism of action and
binding site and provides well-balanced inhibition of two different
Type II topoisomerase enzymes. This provides activity against most
strains of target uropathogens, such as E. coli and Staphylococcus saprophyticus, including
isolates resistant to current antibiotics. Furthermore, due to the
well-balanced inhibition of two enzymes, mutations in both enzymes
are needed to significantly affect susceptibility to
gepotidacin.
GSK in antimicrobials
The
Company is committed to investing in solutions to help get ahead of
antimicrobial resistance. GSK is already a leader on the
Antimicrobial Resistance Benchmark of the Access to Medicine
Foundation. As well as a legacy in antibiotics, GSK has a growing
late-stage pipeline of antimicrobials alongside gepotidacin for the
potential treatment of UTI. In September 2022, GSK entered into an
exclusive licence agreement with Spero Therapeutics to add a
late-stage antibiotic, tebipenem HBr, to potentially treat
complicated urinary tract infections (cUTI) to GSK's pipeline. In
addition, in March 2023, GSK entered into an exclusive licence
agreement with SCYNEXIS, Inc to add a US FDA-approved,
first-in-class antifungal Brexafemme (ibrexafungerp) for
the treatment of vulvovaginal candidiasis in adult and
post-menarchal pediatric females to
GSK's growing portfolio of antimicrobials. The transaction is
subject to the expiration of the waiting period under the
Hart-Scott-Rodino Antitrust Improvements Act of 1976, as
amended.
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 https://www.gsk.com/en-gb/company/.
GSK enquiries
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Investor
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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 under Item 3.D 'Risk
factors" in the company's Annual Report on Form 20-F for 2022,
GSK's Q4 Results for 2022 and any impacts of the COVID-19
pandemic.
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Office:
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9GS
[1] Historic
self-reported data from a survey sample of 2000 women in the US. 1.
Foxman, 2000, 2. Foxman, 2003
[2] Hooton TM.
Uncomplicated Urinary Tract Infection. N Engl J Med.
2012;366:1028-37.
[3] Rich SN,
Klann EM, Almond CR, Larkin EM, Nicolette G, Ball JD. Associations
between antibiotic prescriptions and recurrent urinary tract
infections in female college students. Epidemiology and Infection.
2019;147.
[4] Medina M,
Castillo-Pino E. An introduction to the epidemiology and burden of
urinary tract infections. Therapeutic Advances in Urology.
2019;11:175628721983217.
[5] Kaye KS, et
al. Antimicrobial resistance trends in urine Escherichia coli
isolates from adult and adolescent females in the United States
from 2011 to 2019: rising ESBL strains and impact on patient
management. Clin Infect Dis 2021;73:1992-1999. doi:
10.1093/cid/ciab560
[6] Trautner et
al. Risk Factors Associated With Antimicrobial Resistance and
Adverse Short-Term Health Outcomes Among Adult and Adolescent
Female Outpatients With Uncomplicated Urinary Tract
Infection
[7] Data on
file
SIGNATURES
Pursuant
to the requirements of the Securities Exchange Act of 1934, the
registrant has duly caused this report to be signed on its behalf
by the undersigned, thereunto duly authorised.
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GSK plc
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(Registrant)
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Date: April
17, 2023
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By:/s/ VICTORIA
WHYTE
--------------------------
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Victoria Whyte
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Authorised
Signatory for and on
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behalf
of GSK plc
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