Blueprint
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 23 November 2016
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 23 November 2016, London UK - LSE
Announcement
GSK announces phase lll study of mepolizumab meets co-primary
endpoints and all secondary endpoints in patients with eosinophilic
granulomatosis with polyangiitis
GlaxoSmithKline plc
(LSE/NYSE: GSK) today announced that both co-primary endpoints and
all secondary endpoints were met in a pivotal phase III study
investigating the efficacy and safety of mepolizumab, an IL-5
antagonist, in patients with relapsing and refractory Eosinophilic
Granulomatosis with Polyangiitis (EGPA), a rare disease
characterised by widespread inflammation in the walls of small
blood vessels (vasculitis).
A key goal of treatment for EGPA is to induce and
maintain remission while reducing the use of corticosteroids and
other immunosuppressive therapies. The co-primary endpoints for
this 52-week study assessed the total duration of remission and the
proportion of patients that achieved sustained remission following
treatment with mepolizumab compared to treatment with placebo, both
on top of standard of care. Remission for these two endpoints was
defined by a Birmingham Vasculitis Activity Score (BVAS), a scoring
system to assess disease activity, of 0 and corticosteroid
dose <4mg/day
prednisolone/prednisone. The difference between the two treatment
groups was statistically significant for both co-primary endpoints
as defined, respectively, by:
- The duration of
remission as defined by the proportion of patients achieving at
least 24 weeks duration of remission, one of five pre-defined
categories of duration, was 19/68 (28%) for mepolizumab and 2/68
(3%) for placebo (P<0.001).
- The proportion
of patients achieving remission at both weeks 36 and 48 of the
study treatment period. This was 22/68 (32%) for mepolizumab and
2/68 (3%) for placebo (P<0.001).
The
study included six secondary endpoints investigating relapse,
remission and corticosteroid use, all considered clinically
relevant for patients with EGPA. Patients demonstrated
statistically significant differences, in favour of mepolizumab,
for all secondary endpoints compared to placebo.
Steve
Yancey, Vice President and Medicine Development Lead for
mepolizumab, GSK said: "We are very pleased to observe the positive
benefits of treatment with mepolizumab across several clinically
relevant measures in this first ever double-blind,
placebo-controlled study in patients with Eosinophilic
Granulomatosis with Polyangiitis. Given that patients with this
rare systemic inflammatory disease have limited treatment options,
these results represent a significant step forward in our efforts
to help them. We now look forward to progressing our
regulatory submission plans."
Most
frequent on-treatment serious adverse events reported for
mepolizumab and placebo, respectively were asthma (4%, 4%),
influenza (0, 3%) and pneumonia (0, 3%). One death was reported in
a patient receiving mepolizumab which was not considered by the
investigator to be related to study treatment.
Mepolizumab is not
approved for use anywhere in the world for EGPA.
It 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.
Nucala®
is a registered trade mark of the GSK
group of companies.
Results
of this study in patients with relapsing and refractory EGPA will
support GSK's plans to submit regulatory applications for this
patient population, expected in 2017. Full results from
the study, including data from the secondary endpoints, will be
submitted for presentation at an upcoming scientific congress and
for publication in a peer-reviewed journal.
The
study was conducted as part of an agreement between GSK and the
National Institute of Allergy and Infectious Diseases (NIAID), part
of the U.S. National Institutes of Health, demonstrating an example
of industry - public body collaboration in the field of rare
disease drug development. Through this collaboration the
mechanisms that underlie EGPA were also investigated, with
potential future benefits for patients.
About
Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss
Syndrome)
EGPA,
previously known as Churg-Strauss syndrome, is one of the
rarest systemic vasculitic (inflammation of blood vessel walls)
diseases. The global incidence is generally reported to be in the
range 1.0 - 4.0 per million, with an estimated prevalence of
approximately 14 - 45 per million. The mean age of diagnosis is 48
years. EGPA can affect multiple organs, including the heart, lungs,
skin, gastrointestinal tract, kidneys, and nervous system, with
varying symptoms, depending on which organs are affected, and to
what extent. The disease can be life-threatening for some patients.
While symptoms vary from one patient to another, almost all have
asthma and/or nasal sinus polyps and blood eosinophilia.
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 with 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
study
The
pivotal phase III study, MEA115921, was a randomised, double-blind
study with the purpose to investigate the efficacy and safety of
mepolizumab 300mg (administered subcutaneously every 4 weeks)
compared with placebo over a 52-week study treatment period in 136
patients with relapsing or refractory EGPA receiving standard of
care therapy including background corticosteroid therapy with or
without immunosuppressive therapy.
About
mepolizumab
Mepolizumab is a
humanised IgG monoclonal antibody specific for interleukin 5
(IL-5). It is one of the ~40 assets profiled to investors at GSK's
R&D event in November 2015 and belongs to 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.
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.
Important
safety information
The following information is based on the Highlights section of the
US Prescribing Information for Nucala (mepolizumab). 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., 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, 10% of subjects who received Nucala
experienced systemic (allergic and nonallergic) and local site
reactions compared to 7% 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.
Injection
Site Reactions: Injection site reactions (e.g. pain, erythema,
swelling, itching, and 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
A pregnancy exposure registry monitors pregnancy outcomes in women
exposed to Nucala
during pregnancy. Healthcare
providers can enrol patients or encourage patients to enrol
themselves by calling 1-877-311-8972 or visiting
www.mothertobaby.org/asthma.
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.
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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
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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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
'Risk factors' in the company's Annual Report on Form 20-F for
2015.
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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.
GlaxoSmithKline plc
(Registrant)
Date: November
23, 2016
By: VICTORIA
WHYTE
----------------------
Victoria Whyte
Authorised
Signatory for and on
behalf
of GlaxoSmithKline plc