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 September 2024
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 . . . . . . . .
Issued: 09
September 2024, London
UK
Depemokimab late-breaking data presented at ERS show a 54%
reduction in severe asthma exacerbations
●
SWIFT-1 and SWIFT-2 phase III
data show depemokimab delivered a statistically
significant and clinically meaningful reduction in exacerbations
over 52 weeks versus placebo plus standard of care, in
duplicate studies
●
Ultra-long-acting
biologic, depemokimab, administered once every six months produced
sustained suppression of a key marker of type 2 inflammation, a
driver of asthma attacks and hospitalisations
●
Data published simultaneously in
the New England Journal of
Medicine
GSK plc (LSE/NYSE: GSK) today presented the full results from the
SWIFT-1 and SWIFT-2 phase III clinical trials which assessed the
efficacy and safety of depemokimab versus placebo in adults and
adolescents with severe asthma with
type 2 inflammation characterised by raised blood eosinophil
count.1 The
data were presented at the European Respiratory Society
International Conference (7-11 September) in Vienna, Austria and
simultaneously published in the New England
Journal of Medicine.
SWIFT-1 and SWIFT-2 are duplicate studies with the same primary and
secondary endpoints. Both trials met their primary endpoints with
statistically significant reductions in the annualised rate of
clinically significant exacerbations (asthma attacks) over 52 weeks
versus placebo, with the pre-specified pooled analysis showing a
significant 54%
reduction in exacerbations [Rate Ratio 0.46, 95% CI, 0.36 - 0.59,
p<0.001] (AER depemokimab = 0.51 exacerbations per
year versus placebo
= 1.11).1
In the pooled analysis of SWIFT-1 and SWIFT-2, there was a 72%
reduction [RR 0.28, 95% CI 0.13 - 0.61, p=0.002]
(AER: depemokimab = 0.02 versus placebo
= 0.09) in the secondary endpoint of clinically significant
exacerbations requiring hospitalisation or emergency department
visit compared to placebo.1 As
the pooled analysis of SWIFT-1 and SWIFT-2 did not control for
multiple comparisons, results with a significant p-value (<0.05)
are termed nominally significant. In the individual trials, the
secondary endpoints assessing quality-of-life or the symptoms-based
measure, showed improvements but did not reach statistical
significance versus placebo.1
These data are part of GSK's aspirations to advance treatment
goals for those with severe asthma. Preventing exacerbations,
a known risk for hospitalisation, and cause of cumulative lung
damage and disease progression, has been a longstanding goal of
asthma treatment and care.2 Sustained
suppression of type 2 inflammation, an underlying driver of
exacerbations, could help change the course of
disease.3 Extended
dosing intervals could also help tackle other barriers to optimal
outcomes such as adherence or frequent healthcare
appointments.4-7
Kaivan Khavandi, SVP, Global Head of Respiratory/Immunology
R&D, said: "With
a dosing schedule of just two injections per year, depemokimab has
the potential to be the first approved ultra-long-acting
biologic with six-month dosing. This could offer physicians
and millions of patients with severe asthma an option that provides
reassurance of sustained suppression of a key marker of type 2
inflammation and a reduction in the rate of exacerbations and
hospitalisation - the fundamental treatment goal in
asthma."
David Jackson, FRCP, MSc, PhD, lead author of SWIFT-1 and
SWIFT-2, Professor
of Respiratory Medicine at King's College London and Clinical
Lead for Severe Asthma at Guy's and St Thomas' Hospitals,
London, said: "As
a physician, it is encouraging to see results of research that
could evolve the management of severe asthma. For me, preventing
exacerbations and particularly those that lead to hospitalisations
is a treatment priority for the people I see with severe asthma.
Not only are exacerbations traumatic for patients, and contribute
to pressures on healthcare systems/hospitals, but each exacerbation
can cause irreversible changes to the tissue of the lungs that over
time can lead to permanent loss of lung function and make a
patient's breathing progressively more difficult."
Depemokimab
is the first ultra-long-acting biologic to be evaluated in phase
III trials; it has high binding affinity and potency for
interleukin-5 (IL-5), which will enable six-month dosing intervals for
patients with severe asthma.1 IL-5 is a key cytokine (protein) in
type 2 inflammation, typically detected by raised blood eosinophil
count.1 More than 80% of people with severe
asthma exhibit type 2 inflammation as the underlying pathobiology
of their asthma. Identification of these people could guide
physicians in initiating the right treatment for the individual's
type of asthma, thereby helping to reduce their risk of
exacerbations.3
The proportion of patients experiencing any adverse event (AE) was
similar between the depemokimab and placebo group in SWIFT-1
(depemokimab = 73%, placebo = 73%) and SWIFT-2 (depemokimab = 72%,
placebo = 78%). No deaths or serious AEs were determined to be
related to the study treatment by the
investigator.1
The trial was conducted during a time of high COVID prevalence, and
these events were recorded as the most common AE across
groups.1 There was no difference in reports of COVID
between those receiving depemokimab or placebo in SWIFT-1
(depemokimab = 20%, placebo = 22%) and SWIFT-2 (15% for both
depemokimab and placebo).1 Nasopharyngitis, another name for the common
cold, was the second most common AE in the pooled analysis. The
proportion of patients experiencing a nasopharyngitis AE was lower
in the depemokimab group than the placebo group in SWIFT-1
(depemokimab = 12%, placebo = 19%) and in SWIFT-2 (depemokimab =
13%, placebo = 21%). Safety analysis of the data continues as
part of the open-label extension studies.1
These data will inform regulatory
filings around
the world. Depemokimab is currently not approved anywhere in the
world.
About the depemokimab development programme
The phase III programme consists of SWIFT-1
and SWIFT-2 in severe
asthma, with
an open label extension study (AGILE).1,8 SWIFT-1
and SWIFT-2 were replicate 52-week, randomised, double-blind,
placebo-controlled, parallel-group, multi-centre clinical
trials.1 The
trials assessed the efficacy and safety of depemokimab adjunctive
therapy in 382 and 380 participants who were randomised to receive
depemokimab or a placebo respectively, in addition to their
standard of care treatment
with medium to high-dose inhaled corticosteroids plus at least one
additional controller.1 Number
of subjects included in the Full Analysis of SWIFT-1: depemokimab =
250, placebo = 132 and in SWIFT-2: depemokimab = 252, placebo =
128.1
The primary endpoint of reduction
in the annualised rate of clinically significant exacerbations
(asthma attacks) over 52 weeks vs. placebo for
the individual studies were as follows:1
●
SWIFT-1:
58% (RR 0.42 [95% CI 0.30, 0.59]; p<0.001)
o
AER
= 0.46 annual exacerbation rate in the depemokimab group vs. 1.11
in the placebo group.
●
SWIFT-2:
48% (RR 0.52 [95% CI 0.36, 073]; p<0.001)
o
AER
= 0.56 annual exacerbation rate in the depemokimab group vs. 1.08
in the placebo group.
An
additional study (NIMBLE) is underway to assess the efficacy and
safety of depemokimab when participants with severe asthma are
switched from mepolizumab or
benralizumab.9
Depemokimab's
half-life and high potency for IL-5 means it has the potential to provide
sustained inhibition of broad inflammatory functions and is being
investigated in a variety of type 2 inflammatory
conditions.1,8-13 Depemokimab is currently being
evaluated in phase III trials across a range of other
IL-5 mediated diseases,
including OCEAN for eosinophilic granulomatosis with polyangiitis
(EGPA)10,
ANCHOR 1 & 2 for chronic rhinosinusitis with nasal polyps
(CRSwNP)11,12 and DESTINY for hypereosinophilic
syndrome (HES).13
About severe asthma and type 2 inflammation
Severe asthma is defined as asthma that requires treatment with
high-dose inhaled corticosteroids plus a second controller (and/or
systemic corticosteroids) or biologic therapy, to prevent it from
becoming 'uncontrolled' or which remains 'uncontrolled' despite
treatment.2 Estimates
suggest that severe asthma accounts for more than 60% of all
asthma-related costs in some countries, with higher per-patient
costs than for a patient with type 2 diabetes or a
stroke.14 Patients
with severe asthma bear a significant financial burden, for medical
care and lost earnings. With some exacerbations leading to sick
days or hospitalisation.14 In
more than 80% of patients with severe asthma, their condition is
driven by type 2 inflammation in which
patients exhibit
elevated levels of eosinophils (a type of white blood
cell).3 Blood
eosinophils count can be measured via a simple blood
test. IL-5 is a core cytokine
(protein) in type 2 inflammation alongside IL-4 and
IL-13.2 Type
2 inflammation drives the underlying pathology various
immune-mediated conditions. IL-5 is responsible for the growth,
activity, and survival of eosinophils.2
About GSK in respiratory
GSK is
redefining the future of respiratory medicine as it builds on
decades of pioneering work to deliver more ambitious treatment
goals and develop the next-generation standard of care, for
hundreds of millions of people with respiratory diseases. With an
industry-leading respiratory portfolio and pipeline of vaccines,
targeted biologics, and inhaled medicines, we are focused on
improving outcomes and the lives of people living with all types of
asthma and COPD along with less understood diseases like refractory
chronic cough or rarer conditions like systemic sclerosis with
interstitial lung disease. GSK is harnessing the latest science and
technology with the aim to modify underlying disease dysfunction
and prevent disease progression.
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 under Item 3.D
"Risk factors" in GSK's Annual Report on Form 20-F for 2023, and
GSK's Q2 Results for 2024.
Registered in England & Wales:
No.
3888792
Registered Office:
980
Great West Road
Brentford,
Middlesex
TW8
9GS
References:
1. Jackson
DJ, et al. Six Monthly Depemokimab in Severe Asthma With an
Eosinophilic Phenotype. NEJM. Published on September 9 at
NEJM.org DOI:
10.1056/NEJMoa2406673
2. Global
Initiative for Asthma. Global Strategy for Asthma Management and
Prevention,2024. Updated May 2024. Available at: https://ginasthma.org/. Accessed
May 2024.Buchheit
KM, et al. Mepolizumab targets multiple immune cells in
aspirin-exacerbated respiratory disease. J
Allergy Clin Immunol.
2021;148(2):574-584.
3.
Heaney L, et al. Eosinophilic
and Noneosinophilic Asthma: An Expert Consensus Framework to
Characterize Phenotypes in a Global Real-Life Severe Asthma
Cohort. Chest.
2021;160(3):814-830.
4. Barretto
KT, et al. Human airway epithelial cells express a functional IL-5
receptor. Allergy.
2020;75(8):2127-2130.
5. Bajbouj
K, et al. IL-5 receptor expression in lung fibroblasts: Potential
role in airway remodelling in asthma. Allergy.
2023;78(3):882-885.
6. Siddiqui
S, et al. Eosinophils and tissue remodeling: Relevance to airway
disease. J
Allergy Clin Immunol.
2023;152(4):841-857.
7. Bergantini
L, et al. Regulatory T cell monitoring in severe eosinophilic
asthma patients treated with mepolizumab. Scand
J Immunol.
2021;94(1):e13031.
8. ClinicalTrials.gov. An
Open-Label Extension Study of GSK3511294 (Depemokimab) in
Participants Who Were Previously Enrolled in 206713 (NCT04719832)
or 213744 (NCT04718103) (AGILE). Available at: https://clinicaltrials.gov/study/NCT05243680 Last
accessed May 2024.
9. ClinicalTrials.gov. A
Study of GSK3511294 (Depemokimab) Compared With Mepolizumab or
Benralizumab in Participants With Severe Asthma With an
Eosinophilic Phenotype (NIMBLE). Available at: https://clinicaltrials.gov/study/NCT04718389 Accessed
May 2024.
10. ClinicalTrials.gov. Efficacy
and Safety of Depemokimab Compared With Mepolizumab in Adults With
Relapsing or Refractory Eosinophilic Granulomatosis With
Polyangiitis (EGPA) Available at: https://clinicaltrials.gov/study/NCT05263934 Accessed
May 2024.
11. ClinicalTrials.gov. Efficacy
and Safety of Depemokimab (GSK3511294) in Participants With Chronic
Rhinosinusitis With Nasal Polyps (ANCHOR-1) Available
at: https://clinicaltrials.gov/study/NCT05274750 Accessed
May 2024
12. ClinicalTrials.gov. Efficacy
and Safety of Depemokimab (GSK3511294) in Participants With Chronic
Rhinosinusitis With Nasal Polyps (ANCHOR-2) Available
at: https://clinicaltrials.gov/study/NCT05281523 Accessed
May 2024.
13. ClinicalTrials.gov. Depemokimab
in Participants With Hypereosinophilic Syndrome, Efficacy, and
Safety Trial (DESTINY) Available
at: https://clinicaltrials.gov/study/NCT05334368
Accessed May 2024.
14. Israel,
E, et
al. Severe and
Difficult-to-Treat Asthma in Adults. N Engl J Med
2017;377:965-76.
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: September
09, 2024
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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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