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
17 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:
17
th
May
2017, London, UK - LSE Announcement
GSK announces NEJM publication of positive phase III study
investigating mepolizumab in patients with Eosinophilic
Granulomatosis with Polyangiitis (EGPA)
Double-blind, placebo-controlled study of mepolizumab in patients
with EGPA demonstrates increased likelihood of remission and
reduced need for corticosteroids when mepolizumab is added to
existing standard of care (SOC)
GSK
today announced publication in the
New England Journal of Medicine
, of a
randomised, double-blind, placebo controlled study investigating
the efficacy and safety of mepolizumab, an IL-5 antagonist, vs
placebo as an add-on therapy in patients with relapsing and/or
refractory Eosinophilic Granulomatosis with Polyangiitis (EGPA).
EGPA is a rare disease characterised by widespread inflammation in
the walls of small blood vessels (vasculitis) which may affect
multiple organ systems and be associated with fatigue, fever and
weight loss.
The
study was a collaboration between GSK and the National Institute of
Allergy and Infectious Diseases (NIAID), part of the U.S. National
Institutes of Health (NIH). Headline data from the study were
previously announced in November 2016.
Efficacy results
In the
52-week pivotal phase III study, mepolizumab treatment demonstrated
efficacy based on both co-primary efficacy endpoints and all
secondary endpoints. Treatment with mepolizumab was in addition to
standard of care (glucocorticoids with or without
immunosuppressants).
Patients
treated with mepolizumab had a significantly greater accrued time
in remission (defined as a prednisolone/prednisone dose of
≤4mg/day and a Birmingham Vascular Activity Score = 0) over
the 52-week treatment period compared to placebo, with 28% of
patients on mepolizumab achieving remission for at least 24 weeks
versus 3% on placebo (p<0.001). In addition, a higher proportion
of patients in the mepolizumab group were in remission at both
Weeks 36 and 48 compared to the placebo group (32% versus 3%;
p<0.001).
More
patients treated with mepolizumab achieved remission within the
first 24 weeks of the study and remained in remission until Week 52
compared to those receiving placebo (19% versus 1%; p=0.007). Over
52 weeks, time to first relapse was significantly longer for
patients on mepolizumab (p<0.001); time to first major relapse
was also longer for patients treated with mepolizumab compared to
placebo (p=0.042). Patients treated with mepolizumab were also able
to achieve significantly lower average doses of
prednisolone/prednisone during Weeks 48 to 52 compared to placebo,
with 44% able to taper their dose to ≤4mg/day versus 7% on
placebo (p<0.001).
A total
of 47% of mepolizumab-treated patients versus 81% of
placebo-treated patients did not achieve protocol-defined
remission. Approximately half the participants in the mepolizumab
group had a relapse, nonetheless a 50% lower rate of relapse with
mepolizumab treatment was seen than was observed with placebo in
this trial (1.14 per year for the mepolizumab group versus 2.27 per
year for the placebo group), which highlights the high morbidity
and challenge of managing patients with this progressive
disease.
Safety results
There
was no difference between the two treatment groups in the
proportion of patients experiencing on-treatment adverse events
(97% versus 94%) and overall the adverse event profile for
mepolizumab was similar to that seen in previous studies with no
new safety signals observed. Fewer patients in the mepolizumab
group reported serious adverse events versus those in the placebo
group (18% versus 26%), with the most frequently reported being
asthma worsening/exacerbation (3% versus 6%). Systemic reactions
were infrequent and reported with higher incidence in the
mepolizumab group compared to placebo. One death was reported in a
patient receiving mepolizumab which was not considered by the
investigator to be related to study treatment.
Dr.
Michael E Wechsler, Professor of Medicine at National Jewish Health
in Denver, Colorado, US, Principal Investigator and lead author of
the study said: “EGPA patients suffer from recurrent relapses
that place these patients at greater risk of permanent tissue and
organ damage. There are currently no therapies specifically
approved for EGPA. While systemic corticosteroids form the
cornerstone of EGPA treatment, they can be associated with
significant side effects. In this study, mepolizumab met several
important clinical goals in the treatment of EGPA: it increased
accrued time in remission, reduced frequency of relapse and
exacerbation, and enabled patients to reduce corticosteroid dose.
These data confirm the potential of mepolizumab as a future
treatment option for patients with this rare
disease.”
Steve
Yancey, Vice-President and Medicines Development Lead for
mepolizumab, GSK, commented: “Uncontrolled eosinophilic
inflammation leads to an unpredictable condition for patients who
often fear the relapses that are a common feature of the disease.
Our goal is to provide patients and healthcare professionals with a
new treatment option to help control this disease. The success of
this study is a testament to the hard work of the GSK team, the
NIAID, and the investigators, and we thank all the patients whose
participation enabled the study to proceed.”
Results
of this study in patients with relapsing and refractory EGPA will
support GSK’s plans to submit regulatory applications,
expected later in 2017.
Mepolizumab
is not approved for use anywhere in the world for
EGPA.
Results of the study are available at:
http://www.nejm.org/doi/full/10.1056/NEJMoa1702079?query=featured_home
In
addition, full results of the study are being presented during the
American Thoracic Society meeting:
-
9.15-11.15am
21
st
May -
NEJM-JAMA session
:
Discussion on the Edge: Reports of
Recently Published Pulmonary Research
-
9.15-11.15am
22
nd
May -
Oral presentation
:
Mepolizumab for the Treatment of
Patients with Eosinophilic Granulomatosis with Polyangiitis: A
Phase III Randomized, Placebo-Controlled Trial.
About the study
The
pivotal phase III study was a randomised, double-blind placebo
controlled study designed to investigate the efficacy and safety of
mepolizumab 300mg (administered subcutaneously every 4 weeks)
compared to placebo, in patients already receiving standard of
care, over a 52-week study treatment period. The study was
conducted in 31 academic centres and hospitals across nine
countries and enrolled 136 patients (mepolizumab n = 68; placebo =
68) with relapsing or refractory EGPA receiving standard of care
therapy (i.e. treatment for more than four weeks on stable dose
prednisolone/prednisone ≥7.5mg - ≤50mg day) with or
without immunosuppressive therapy. The study population was
representative of patients with EGPA treated with glucocorticoids
with or without additional immunosuppressant therapy.
Study endpoints
The
co-primary endpoints were the total accrued weeks of remission over
the full trial period, and the proportion of patients in remission
at both Weeks 36 and 48. Remission was defined by a Birmingham
Vasculitis Activity Score (BVAS), a scoring system to assess
disease activity, of zero, and a prednisolone/prednisone dose
≤4mg/day.
The
study included six secondary endpoints investigating relapse,
remission and corticosteroid use, all considered clinically
relevant for patients with EGPA.
About EGPA (previously known as Churg-Strauss
Syndrome)
Eosinophilic
granulomatosis with polyangiitis (EGPA) is a rare disease that
causes inflammation of the small blood vessels (or vasculitis). The
global incidence is generally reported to be in the range 1–4
per million, with an estimated prevalence of approximately
14–45 per million. The mean age of diagnosis is 48 years and
the disease can be life-threatening for some patients.
In EGPA, patients usually develop asthma initially, before the
vasculitis extends to inflammation of the small blood vessels that
supply tissues in the lungs, sinuses, skin, nerves and other
organs. EGPA can result in damage to almost every organ in the body
and the symptoms common to most include extreme fatigue, weight
loss, muscle and joint pain, sinonasal symptoms and breathlessness,
all of which affect patients’ ability to carry out everyday
activities without difficulty.
The current approach to disease management is primarily based on
reduction of active inflammation and suppression of the immune
response through the use of corticosteroid therapy and concomitant
immunosuppressive therapy (e.g., methotrexate, azathioprine,
mycophenolate mofetil) and/or cytotoxic agents (e.g.,
cyclophosphamide). Although the use of these treatments can be
effective for establishing remission, patients remain vulnerable to
either the complications of the long-term use of these therapies,
or to the risk of relapse, particularly if the dose of
corticosteroid is reduced.
About mepolizumab
Mepolizumab
is a humanised IgG monoclonal antibody specific for interleukin 5
(IL-5). IL-5 is a cytokine which regulates the growth, activation
and survival of eosinophils (white blood cells) and provides an
essential signal for the movement of eosinophils from the bone
marrow into the lung and other organs. Mepolizumab binds to
human IL-5, stopping it from binding to its receptor on the surface
of eosinophils. Inhibiting IL-5 binding in this manner reduces
blood, tissue and sputum eosinophil levels, which in turn reduces
eosinophil-mediated inflammation.
Mepolizumab
is not approved anywhere in the world for EGPA. Mepolizumab is
approved for use in the E.U., under the brand name Nucala, for use
as an add-on treatment for severe refractory eosinophilic asthma in
adult patients.
Nucala is approved for
use in the U.S. as an add-on maintenance treatment of patients with
severe asthma aged 12 years and older, and with an eosinophilic
phenotype. It is not approved for the treatment of other
eosinophilic conditions or relief of acute bronchospasm or status
asthmaticus.
Nucala
has also been approved in Canada, Australia, Japan, Switzerland,
Chile, South Korea and Taiwan. Trade marks are owned by or licensed
to the GSK group of companies.
Important Safety Information for Nucala in Severe Eosinophilic
Asthma
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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Fiona
McMillan
|
+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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Anna
Padula
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+1 215
751 4271
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(Philadelphia)
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Sarah
Spencer
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+1 215
751 3335
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(Philadelphia)
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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)
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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
|
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
17, 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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