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 10 May
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:
Wednesday 10 May 2017, London UK
GSK announces headline phase III results of mepolizumab in patients
with severe chronic obstructive pulmonary disease
GlaxoSmithKline
plc (LSE/NYSE:GSK) today announced preliminary results of two
pivotal phase III studies evaluating the efficacy and safety of
mepolizumab, an IL-5 antagonist monoclonal antibody, as an
investigational add on treatment for adults who have chronic
obstructive pulmonary disease (COPD) with an eosinophilic
phenotype.
The
primary objective of the 52-week treatment studies was to
investigate whether reducing eosinophils (a type of white blood
cell) with subcutaneous mepolizumab 100mg and 300mg would decrease
the frequency of moderate and severe exacerbations in COPD patients
at high risk of exacerbations despite use of optimal standard of
care therapy.
- Study 117106 (METREX) randomised 836 patients to mepolizumab
100mg or placebo across two groups
according to blood eosinophil count. In the group 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).
- Study 117113 (METREO) randomised 674 patients to mepolizumab
100mg, mepolizumab 300mg or placebo. 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).
Steve
Yancey, Vice President and Medicine Development Lead for
mepolizumab, GSK said: "We embarked on these two studies in our
pursuit to help COPD patients with an eosinophilic phenotype who
still exacerbate despite optimal use of medicines available today.
We believe the reduction in moderate and severe exacerbations
observed are of clinical relevance given the need for a new
treatment approach in these difficult to treat patients. We will
review the full data when available to determine our next
steps."
Full
results will be submitted for presentation at an upcoming
scientific congress and for publication in a peer-reviewed
journal.
No
safety concerns were identified on review of headline 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 81% in the placebo group and 79% in
the mepolizumab 100mg group and the frequency of serious adverse
events was 28% in the placebo group and 25% in the mepolizumab
100mg group. In the METREO study, the frequency of adverse events
was 81% in the placebo group, 83% in the mepolizumab 100mg group
and 85% in the mepolizumab 300mg group and the frequency of serious
adverse events was 26% in the placebo group, 23% in the mepolizumab
100mg group and 24% in the mepolizumab 300mg group.
Study Design
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) evaluated 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.
The
METREO study (117113) evaluated mepolizumab 100mg, mepolizumab
300mg or placebo in patients with a blood eosinophil count of
>150 cells/µl at study entry or >300 cells/µl
within the past year (higher eosinophil group).
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 humanised IgG1 monoclonal antibody specific for IL-5. It is
part of the company's respiratory portfolio - one of six core areas
of scientific research and development alongside
immuno-inflammation, oncology, vaccines and infectious and rare
diseases.
Mepolizumab
is the first-in-class anti-IL-5 biologic therapy. It was initially
developed to treat appropriate severe asthma patients whose
condition is driven by inflammation caused by eosinophils.
Mepolizumab binds to the signalling protein IL-5, preventing it
from binding to its receptor on the surface of eosinophils.
Inhibiting IL-5 binding in this way reduces blood, tissue and
sputum eosinophil levels.
Mepolizumab
is not approved for use anywhere in the world for
COPD.
Mepolizumab
is approved, under the brand name Nucala, in the EU, the US and a
number of other countries for use as an add-on treatment for
patients with severe asthma, with an eosinophilic
phenotype.
In the
US, Nucala (100mg fixed dose subcutaneous injection of mepolizumab)
is licensed as an add-on maintenance treatment for patients with
severe asthma aged 12 years and older, and with an eosinophilic
phenotype. Nucala is not approved for the treatment of other
eosinophilic conditions or relief of acute bronchospasm or status
asthmaticus. Full US Prescribing Information is available at
US
Prescribing Information Nucala.
In the
EU, Nucala (100mg fixed dose subcutaneous injection of mepolizumab)
is licensed as an add-on treatment for severe refractory
eosinophilic asthma in adult patients. For the EU Summary of
Product Characteristics for Nucala, please visit: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003860/WC500198037.pdf
Mepolizumab
is also being investigated in eosinophilic granulomatosis with
polyangiitis (EPGA, also referred to as Churg-Strauss syndrome, in
phase
III), severe hypereosinophilic syndrome (in phase III),
nasal polyposis (phase II) and severe atopic dermatitis (phase
II).
Nucala
has also been approved in Canada, Australia, Japan, Switzerland,
Chile, South Korea and Taiwan for severe asthma, with an
eosinophilic phenotype. Further regulatory applications in this
indication have been submitted and are under review in other
countries.
Nucala®
is a registered trade mark of the GSK group of
companies.
Important Safety Information for Nucala
The
following information is based on the US Prescribing Information
for Nucala. 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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Namrata
Taak
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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
Alspach
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+1 202
715 1048
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(Washington,
DC)
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Sarah
Spencer
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+1 215
751 3335
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(Philadelphia)
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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
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 '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: May
10, 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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