FORM 6-K
SECURITIES AND EXCHANGE COMMISSION
Washington D.C. 20549
Report of Foreign Issuer
Pursuant to Rule 13a-16 or 15d-16 of
the Securities Exchange Act of 1934
For
period ending 12 September
2017
GlaxoSmithKline plc
(Name
of registrant)
980 Great West Road, Brentford, Middlesex, TW8 9GS
(Address
of principal executive offices)
Indicate
by check mark whether the registrant files or
will
file annual reports under cover Form 20-F or Form 40-F
Form
20-F x Form 40-F
--
Indicate
by check mark whether the registrant by furnishing the
information
contained in this Form is also thereby furnishing the
information
to the Commission pursuant to Rule 12g3-2(b) under the
Securities
Exchange Act of 1934.
Yes
No x
Issued:
Tuesday 12 September 2017, London UK
GSK announces phase III results published in NEJM of mepolizumab in
patients with eosinophilic COPD at risk of
exacerbations
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Regulatory filings planned for 2017
GlaxoSmithKline
plc (LSE/NYSE: GSK) today announced the publication of full results
from the
phase
III studies for mepolizumab in chronic obstructive pulmonary
disease (COPD). Data from the investigational clinical development
programme showed that treating eosinophilic COPD patients with the
biologic medicine, mepolizumab, in addition to maximal
guideline-recommended therapy, reduced exacerbations in these
difficult-to-treat patients. Based on the full data, discussions
with external experts and the recognised unmet medical need in this
patient population, regulatory filings are planned for 2017.
Mepolizumab is not approved for use anywhere in the world for
COPD.
Results
of the METREX and METREO studies, along with data from a
pre-specified meta-analysis combining both studies, have been
published in the New England Journal of Medicine (NEJM), with
simultaneous presentation at the European Respiratory Society (ERS)
International Congress 2017.
The
studies were designed to evaluate the efficacy and safety of
mepolizumab as add-on therapy in the reduction of moderate to
severe COPD exacerbations in patients at high risk of exacerbations
and to identify the patients with COPD most likely to respond to
treatment using blood eosinophils (a type of white blood cell known
to play a role in some inflammatory diseases) as a biomarker. In
addition, METREO investigated efficacy and safety at different
doses of mepolizumab. Patients included in the studies had a
history of frequent exacerbations, despite receiving optimal
standard of care treatments, with the majority categorised as Stage
D, patients with the most advanced disease, according to the Global
Initiative for Chronic Obstructive Lung Disease (GOLD)
guidelines.
Overall,
COPD patients with blood eosinophil counts of >150 cells/µL at study
entry or >300
cells/µL within the past year treated with add-on 100mg
mepolizumab showed a consistent 18-20% reduction in the primary
endpoint of annual rate of moderate and severe
exacerbations.
● The
reduction in the frequency of exacerbations observed in the METREX
study was statistically significant (18%, p=0.036 after
multiplicity adjustment).
● In
METREO, the reduction was not statistically significant (20%,
p=0.068 after multiplicity adjustment).
The
pre-specified meta-analysis evaluated the association between
screening blood eosinophil counts and treatment response. The
analysis showed that rates of exacerbation reduction increased as
blood eosinophil counts increased, signifying the relevance of
blood eosinophils as a biomarker to help identify COPD patients
most likely to respond to treatment with mepolizumab.
There was no evidence of greater treatment effect in patients
treated with a higher (300mg) dose of mepolizumab investigated in
the dose ranging METREO study. In the METREX study, patients with blood
eosinophil counts of less than 150 cells/µL at the start of
the study (i.e. patients with non-eosinophilic COPD) were not found
to benefit from mepolizumab.
For the
secondary endpoints, there was a statistically significant increase
in the time to first moderate and severe exacerbation in METREX,
with numerical, but not significant, increase in time to first
exacerbation in METREO. There were no significant differences
between mepolizumab and placebo in either study on the remaining
secondary endpoints: annual rate of exacerbations requiring
emergency department visit and/or hospitalisation, St George's
Respiratory Questionnaire score and COPD assessment test
score.
Steve
Yancey, Vice President and Medicine Development Lead for
mepolizumab, GSK said: "We believe the data published today in the
New England Journal of Medicine demonstrate the benefits of a
personalised medicine approach in the treatment of COPD with
mepolizumab, using blood eosinophils as a biomarker. Based on the
clinically meaningful reductions in exacerbations shown in these
studies, we plan to progress regulatory filings this
year."
Professor
Ian Pavord, University of Oxford said: "For people living with
COPD, a sudden worsening of their symptoms, known as an
exacerbation, causes them to struggle to breathe despite receiving
the available guideline recommended treatment. For these patients,
there are currently no other treatment options. When considering
the challenges these patients face, the exacerbation reduction
shown in the METREX and METREO studies is a clinically important
outcome."
No new
safety concerns to the known safety profile of mepolizumab were
identified on review of the data from these studies. The proportion
of patients experiencing adverse events and serious adverse events
while receiving treatment was similar for mepolizumab and placebo.
In the METREX study, the frequency of adverse events was 80% in the
mepolizumab 100mg group and 82% in the placebo group, and the
frequency of serious adverse events was 28% in the mepolizumab
100mg group and 31% in the placebo group. In the METREO study,
the frequency of adverse events was 86% in the mepolizumab 100mg
group, 87% in the mepolizumab 300mg group 82% in the placebo group,
and the frequency of serious adverse events was 26% in the
mepolizumab 100mg group, 27% in the mepolizumab 300mg group and 30%
in the placebo group.
Study Design and Primary Endpoint Results
The
phase III studies were multi-centre, randomised, placebo
controlled, double blind, parallel group design with treatment
administered by subcutaneous (SC) injection every four weeks in
COPD patients at high risk of exacerbations despite the use of
optimal standard of care background therapy which employed inhaled
triple therapy consisting of an inhaled corticosteroid (ICS),
long-acting beta agonist (LABA) and long-acting muscarinic
antagonist (LAMA). The total duration of the studies was
approximately 62 weeks consisting of a 1-2 week screening period,
52-week treatment period and 8-week follow-up
period.
The METREX study (117106) was designed to evaluate mepolizumab
100mg or placebo across a range of baseline blood eosinophil
counts. Patients were stratified according to i) blood eosinophil
count of >150 cells/µL at study entry or
>300 cells/µL within the past year (higher
eosinophil group) or ii) blood eosinophil count of <150
cells/µL at study entry and no evidence of >300 cells/µL within the past year. For the
primary endpoint in patients with higher eosinophils, there was a
statistically significant reduction in the frequency of moderate
and severe exacerbations for mepolizumab 100mg compared to placebo
(18%, p=0.036 after multiplicity adjustment).
The METREO study (117113) was designed as a dose-ranging study.
Patients with a blood eosinophil count of >150 cells/µL at study entry or
>300 cells/µL within the past year (higher
eosinophil group) were randomised to receive mepolizumab 100mg,
mepolizumab 300mg or placebo. For the primary endpoint in patients
with higher eosinophils, a reduction in the frequency of moderate
and severe exacerbations for mepolizumab compared to placebo was
seen which was not statistically significant (20% for 100mg,
p=0.068; 14% for 300mg, p=0.140 after multiplicity
adjustment).
Moderate
exacerbations were defined as those requiring treatment with
systemic corticosteroids and/or antibiotics. Severe
exacerbations were those requiring hospitalisation or resulted in
death.
About mepolizumab
Mepolizumab is a first-in-class monoclonal antibody that targets
the signalling protein IL-5. Mepolizumab binds to IL-5, preventing
it from binding to its receptor on the surface of white blood cells
called eosinophils. Inhibiting IL-5 binding in this way reduces
blood eosinophils.
Eosinophils are believed to play a role in protecting the body
against infection. In some people, eosinophils can cause
inflammation and are involved in the development of some
inflammatory diseases. Mepolizumab has been developed for the
treatment of diseases that are driven by inflammation caused by
eosinophils.
Mepolizumab is not approved for use anywhere in the world for
COPD.
Mepolizumab is approved for use in the US under the brand name
Nucala as an add-on
maintenance treatment for patients with severe asthma aged 12 years
and older, and with an eosinophilic phenotype. Nucala has also been
approved for severe eosinophilic asthma in the EU, Japan and a
number of other countries worldwide, although the details of the
indications may vary.
Mepolizumab
has been submitted for regulatory review for eosinophilic
granulomatosis with polyangiitis (EPGA, also referred to as
Churg-Strauss syndrome) and is being investigated for severe
hypereosinophilic syndrome, nasal polyposis and atopic
dermatitis.
Trademarks are owned by or licensed to the GSK group of
companies.
Important Safety Information for
Nucala in Severe Asthma with an Eosinophilic Phenotype (based on US
Prescribing Information)
Please consult the full Prescribing Information for all the
labelled safety information for Nucala.
CONTRAINDICATIONS
Nucala should not be administered to patients with a history of
hypersensitivity to mepolizumab or excipients in the
formulation.
WARNINGS AND PRECAUTIONS
Hypersensitivity Reactions
Hypersensitivity reactions (e.g. anaphylaxis, angioedema,
bronchospasm, hypotension, urticaria, rash) have occurred following
administration of Nucala. These reactions generally occur within
hours of administration but in some instances can have a delayed
onset (i.e. days). In the event of a hypersensitivity reaction,
Nucala should be discontinued.
Acute Asthma Symptoms or Deteriorating
Disease
Nucala should not be used to treat acute asthma symptoms, acute
exacerbations, or acute bronchospasm.
Opportunistic Infections: Herpes Zoster
In controlled clinical trials, 2 serious adverse reactions of
herpes zoster occurred in subjects treated with Nucala compared to
none in placebo. Consider varicella vaccination if medically
appropriate prior to starting therapy with Nucala.
Reduction of Corticosteroid Dosage
Do not discontinue systemic or inhaled corticosteroids (ICS)
abruptly upon initiation of therapy with Nucala. Decreases in corticosteroid doses, if
appropriate, should be gradual and under the direct supervision of
a physician. Reduction
in corticosteroid dose may be associated with systemic withdrawal
symptoms and/or unmask conditions previously suppressed by systemic
corticosteroid therapy.
Parasitic (Helminth) Infection
It is unknown if Nucala
will influence a patient's response
against parasites. Treat patients with pre-existing helminth
infections before initiating therapy with Nucala. If
patients become infected while receiving treatment with
Nucala and do not respond to anti-helminth treatment,
discontinue treatment with Nucala until
infection resolves.
ADVERSE REACTIONS
The most common adverse reactions (≥3% and more common than
placebo) reported in the first 24 weeks of two clinical trials
with Nucala (and placebo) were: headache, 19% (18%);
injection site reaction, 8% (3%); back pain, 5% (4%); fatigue, 5%
(4%); influenza, 3% (2%); urinary tract infection 3% (2%);
abdominal pain upper, 3% (2%); pruritus, 3% (2%); eczema, 3%
(<1%); and muscle spasm, 3% (<1%).
Systemic Reactions, including Hypersensitivity Reactions: In
3 clinical trials, 3% of subjects who received Nucala experienced systemic (allergic and nonallergic)
reactions compared to 5% in the placebo group. Systemic
allergic/hypersensitivity reactions were reported by 1% of subjects
who received Nucala
compared to 2% of subjects in the
placebo group. Manifestations included rash, pruritus, headache,
and myalgia. Systemic nonallergic reactions were reported by 2% of
subjects who received Nucala and 3%
of subjects in the placebo group. Manifestations included rash,
flushing, and myalgia. A majority of the systemic reactions were
experienced on the day of dosing. Reports of anaphylaxis have been
received postmarketing.
Injection site reactions (e.g. pain, erythema, swelling, itching,
burning sensation) occurred at a rate of 8% in subjects treated
with Nucala compared with 3% in subjects treated with
placebo.
USE IN SPECIFIC POPULATIONS
The
data on pregnancy exposures from the clinical trials are
insufficient to inform on drug-associated risk. Monoclonal
antibodies, such as mepolizumab, are progressively transported
across the placenta in a linear fashion as pregnancy progresses;
therefore, potential effects on a foetus are likely to be greater
during the second and third trimesters of pregnancy.
GSK - one of the world's
leading research-based pharmaceutical and healthcare companies - is
committed to improving the quality of human life by enabling people
to do more, feel better and live longer. For further
information please visit www.gsk.com.
GSK enquiries:
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UK
Media enquiries:
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Simon
Steel
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+44 (0)
20 8047 5502
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(London)
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David
Daley
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+44 (0)
20 8047 5502
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(London)
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US
Media enquiries:
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Sarah
Spencer
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+1 215
751 3335
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(Philadelphia)
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Mary
Anne Rhyne
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+1 919
483 0492
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(North
Carolina)
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Karen
Hagens
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+1 919
483 2863
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(North
Carolina)
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Analyst/Investor
enquiries:
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Sarah
Elton-Farr
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+44 (0)
20 8047 5194
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(London)
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Tom
Curry
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+ 1 215
751 5419
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(Philadelphia)
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Gary
Davies
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+44 (0)
20 8047 5503
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(London)
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James
Dodwell
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+44 (0)
20 8047 2406
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(London)
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Jeff
McLaughlin
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+1 215
751 7002
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(Philadelphia)
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Cautionary statement regarding forward-looking statementsGSK
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
'Principal risks and uncertainties' in the company's Annual Report
on Form 20-F for 2016.
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Registered in England & Wales:
No. 3888792
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Registered Office:
980 Great West Road
Brentford, Middlesex
TW8 9GS
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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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GlaxoSmithKline plc
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(Registrant)
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Date: September
12, 2017
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By: VICTORIA
WHYTE
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Victoria Whyte
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Authorised
Signatory for and on
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behalf
of GlaxoSmithKline plc
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