REG - GSK PLC - Depemokimab late-breaking data presented at ERS

GSKAnnouncement

09/09/2024 14:30

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RNS Number : 4263D  GSK PLC  09 September 2024

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.

 

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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/ (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
(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
(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
(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
(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
(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
(https://clinicaltrials.gov/study/NCT05334368%20Accessed%20May%202024) .

14.    Israel, E, et al. Severe and Difficult-to-Treat Asthma in Adults. N
Engl J Med 2017;377:965-76.

 

 

 

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