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 February
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
GlaxoSmithKline plc (the 'Company')
Issued:
Thursday 23 February 2017 London UK - LSE Announcement
Positive results for Relvar®
Ellipta®
lung function study in patients
with well-controlled asthma
GlaxoSmithKline plc (LSE/NYSE:GSK) and Innoviva, Inc. (NASDAQ: INVA)
today
announced positive headline results from a non-inferiority lung
function study, which demonstrated that patients with
well-controlled asthma were able to switch to the once-daily
Relvar® Ellipta®
(fluticasone
furoate/vilanterol, FF/VI) 100/25, an inhaled corticosteroid
(ICS)/long-acting beta2
agonist (LABA)
combination, from the twice-daily Seretide®
Accuhaler®
(fluticasone
propionate /salmeterol, FP/SAL) 250/50, without compromising their
lung function.
Patients randomised to FF/VI taken once-daily maintained lung
function comparable with those randomised to the twice-daily FP/SAL
[difference +19mL (95% CI: -11mL, +49mL], meeting the study's
primary endpoint, based on the lower bound (-11ml) of the 95%
confidence interval falling above the non-inferiority margin of
-100mL.
A third treatment arm with fluticasone propionate (FP), ICS
monotherapy, was included to detect a lung function difference
between treatments. Results demonstrated statistically significant
differences in favour of the ICS/LABA combinations to FP
(p<0.001).
The incidences of on-treatment serious adverse events (SAEs) and
adverse events (AEs) of special interest were consistent with the
known safety profile of FF/VI, established in asthma patients from
other studies.
Eric Dube, SVP and Global Head of Respiratory Franchise, GSK said:
At GSK we are constantly searching for ways in which we can help
patients better manage their asthma. In this positive study we have
demonstrated non-inferiority for once-daily Relvar versus
twice-daily Seretide on lung function. This gives us confidence
that for patients who struggle taking a twice-daily treatment
regimen, there may be a once-daily treatment option available,
providing greater physician choice to help patients."
Mike
Aguiar, CEO of Innoviva, Inc., added: "We believe the results of
this study are important for patients and physicians. They provide
additional evidence that patients with persistent asthma, who are
currently treated with a twice-daily ICS/LABA, in this case
Seretide, can experience a similar level of benefit in lung
function when treated with Relvar Ellipta, which only needs to be
taken once a day."
The study design was agreed with European regulatory authorities.
GSK now intends to submit this data to the European Medicines
Agency (EMA).
Results from the study will be shared in future publications and
presentations.
Study Design
Following
a 4-week open-label treatment period with FP/SAL 250/50
twice-daily, patients with well controlled asthma were randomised
to receive either FF/VI 100/25 once-daily, FP/SAL 250/50
twice-daily or FP 250 twice-daily in a double-blind, double-dummy
manner for 24 weeks at multiple centres in 12
countries.
The
primary objective of the study was to demonstrate non-inferiority
of Relvar Ellipta 100/25 once-daily with Seretide Accuhaler 250/50
twice-daily in adult and adolescent subjects 12 years of age and
older with persistent bronchial asthma, well controlled on
twice-daily ICS/LABA. The endpoint for the study was the change
from baseline in clinic visit evening FEV1
(pre-brochodilator and pre-dose) at the end of the 24-week
treatment period.
To
demonstrate the non inferiority of FF/VI vs FP/SAL the lower limit
of the 95% confidence interval for the mean difference in change
from baseline for evening FEV1 needed to be
greater than the pre defined margin of -100mL. This was to rule out
the possibility that FF/VI was more than -100mL inferior to
FP/SAL.
About asthma
Asthma
is a chronic lung disease that inflames and narrows the airways.
Asthma affects 358 million people worldwide. Despite medical
advances, more than half of patients continue to experience poor
control and significant symptoms impacting their daily
life.
The
causes of asthma are not completely understood but likely involve
an interaction between a person's genetic make-up and the
environment. Key risk factors are inhaled substances that provoke
allergic reactions or irritate the airways.
About Relvar
Ellipta (fluticasone furoate + vilanterol)
Relvar Ellipta is a once-daily
dual combination treatment comprising fluticasone furoate, an
inhaled corticosteroid and vilanterol, a long-acting
beta2-agonist, in a single inhaler, the
Ellipta®.
Relvar Ellipta is indicated in
Europe in the regular treatment of patients aged 12 and over with
asthma, where use of a combination product (long-acting
ß2-agonist, LABA, and inhaled corticosteroid, ICS) is
appropriate: Patients not adequately controlled on both ICS and
'as-needed' short-acting ß2-agonist
(SABA).
Full EU prescribing information is available at:
EU
Prescribing Information for Relvar Ellipta.
Important safety information for Relvar Ellipta in
Europe
FF/VI is contraindicated in patients with hypersensitivity to
either fluticasone furoate, vilanterol, or any of the
excipients.
FF/VI should not be used to treat acute asthma symptoms or an acute
exacerbation in COPD, for which a short-acting bronchodilator is
required. Increasing use of short-acting bronchodilators to relieve
symptoms indicates deterioration of control and patients should be
reviewed by a physician.
Patients should not stop therapy with FF/VI in asthma or COPD,
without physician supervision since symptoms may recur after
discontinuation.
Asthma-related adverse events and exacerbations may occur during
treatment with FF/VI. Patients should be asked to continue
treatment but to seek medical advice if asthma symptoms remain
uncontrolled or worsen after initiation of treatment with
FF/VI.
Paradoxical bronchospasm may occur with an immediate increase in
wheezing after dosing. This should be treated immediately with a
short-acting inhaled bronchodilator. FF/VI should be discontinued
immediately, the patient assessed and alternative therapy
instituted if necessary.
Cardiovascular effects, such as cardiac arrhythmias e.g.
supraventricular tachycardia and extrasystoles may be seen with
sympathomimetic medicinal products including FF/VI. Therefore
fluticasone furoate/vilanterol should be used with caution in
patients with severe cardiovascular disease.
For patients with moderate to severe hepatic impairment, the
92/22 mcg dose should be used and patients should be monitored
for systemic corticosteroid-related adverse reactions. FF/VI
184/22 mcg is not indicated for patients with COPD. There is
no additional benefit of the 184/22 mcg dose compared to the
92/22 mcg dose and there is a potential increased risk of
pneumonia and systemic corticosteroid-related adverse
reactions.
An increase in the incidence of pneumonia has been observed in
subjects with COPD receiving FF/VI. There was also an
increased incidence of pneumonias resulting in hospitalisation. In
some instances these pneumonia events were fatal.
The incidence of pneumonia in patients with asthma was common at
the higher dose. In a previous study of FF/VI in asthma the
incidence of pneumonia in patients with asthma taking FF/VI
184/22 mcg was numerically higher compared with those
receiving FF/VI 92/22 mcg or placebo.
Hyperglycaemia: There have been reports of increases in blood
glucose levels in diabetic patients and this should be considered
when prescribing to patients with a history of diabetes
mellitus.
Systemic effects may occur with any inhaled corticosteroid,
particularly at high doses prescribed for long periods. These
effects are much less likely to occur than with oral
corticosteroids. Possible systemic effects include Cushing's
syndrome, Cushingoid features, adrenal suppression, decrease in
bone mineral density, growth retardation in children and
adolescents, cataract and glaucoma and more rarely, a range of
psychological or behavioural effects including psychomotor
hyperactivity, sleep disorders, anxiety, depression or aggression
(particularly in children).
FF/VI should be administered with caution in patients with
pulmonary tuberculosis or in patients with chronic or untreated
infections. Data from large asthma and COPD clinical trials were
used to determine the frequency of adverse reactions associated
with FF/VI.
Very common adverse reactions (occurring in >1/10 patients) with
FF/VI were headache and nasopharyngitis. Common adverse reactions
(occurring in >1/100 to <1/10 patients) were pneumonia, upper
respiratory tract infection, bronchitis, influenza, candidiasis of
mouth and throat, oropharyngeal pain, sinusitis, pharyngitis,
rhinitis, cough, dysphonia, abdominal pain, arthralgia, back pain,
fractures, and pyrexia and muscle spasms..Extrasystoles were
observed as an uncommon adverse reaction (occurring in >1/1,000
to <1/100 patients). Rare adverse reactions (occurring in
>1/10,000 to < 1/1,000) were hypersensitivity reactions
(including anaphylaxis, angioedema, rash and urticaria), anxiety,
tremor, palpitations, tachycardia and paradoxical bronchospasm.
With the exception of pneumonia and fractures, the safety profile
was similar in patients with asthma and COPD. During clinical
studies, pneumonia and fractures were more frequently observed in
patients with COPD.
Relvar Ellipta is known as Breo Ellipta in the United
States. Breo Ellipta is licensed in the US for:
●
The
once-daily treatment of asthma in patients aged 18 years and
older.
Long-acting beta2-adrenergic agonists (LABA), such
as vilanterol, one of the active ingredients in Breo
Ellipta, increase the risk of
asthma-related death. Available data from controlled clinical
trials suggest that LABA increase the risk of asthma-related
hospitalization in pediatric and adolescent patients. Therefore,
when treating patients with asthma, physicians should only
prescribe Breo Ellipta for
patients not adequately controlled on a long-term asthma control
medication, such as an inhaled corticosteroid, or whose disease
severity clearly warrants initiation of treatment with both an
inhaled corticosteroid and a LABA. Once asthma control is achieved
and maintained, assess the patient at regular intervals and step
down therapy (e.g., discontinue Breo Ellipta) if possible without loss of asthma control and
maintain the patient on a long-term asthma control medication, such
as an inhaled corticosteroid. Do not use BREO ELLIPTA for patients
whose asthma is adequately controlled on low- or medium-dose
inhaled corticosteroids.
●
Breo Ellipta is NOT indicated for the
relief of acute bronchospasm.
Full US prescribing information, including BOXED WARNING and
Medication Guide is available
at us.gsk.com or US
Prescribing Information for Breo Ellipta.
About Seretide Accuhaler (fluticasone propionate +
salmeterol)
Seretide Accuhaler is a twice-daily dual combination
treatment comprising fluticasone
propionate /salmeterol, in the Accuhaler
inhaler.
Seretide Accuhaler is indicated
in Europe in the regular treatment of patients aged 4 and over with
asthma, where use of a combination product (long-acting
ß2-agonist, LABA, and inhaled corticosteroid, ICS) is
appropriate: Patients not adequately controlled on both ICS and
'as-needed' short-acting ß2-agonist
(SABA); Patients already adequately controlled on both ICS and
LABA.
For the UK Summary of Product
Characteristics (SmPC), please visit: https://www.medicines.org.uk/emc/medicine/2317/SPC/Seretide+100,+250,+500+Accuhaler
Important safety information for Seretide Accuhaler
Uses: Asthma: Regular treatment of asthma, where a
long-acting b2 agonist and
inhaled corticosteroid is appropriate, i.e. patients uncontrolled
on inhaled corticosteroids and 'as needed' short-acting inhaled
bronchodilator or patients controlled on inhaled corticosteroid and
long-acting b2 agonist. Lowest
strength Seretide (salmeterol 25mcg/fluticasone propionate 50
mcg and salmeterol 50mcg/fluticasone propionate 100 mcg) not
appropriate in severe asthma. COPD: Symptomatic treatment of
patients with COPD with a FEV1 <60% predicted normal
(pre-bronchodilator) and a history of repeated exacerbations, who
have significant symptoms despite regular bronchodilator
therapy.
Dosage and administration: Inhalation only. Asthma:
Adults and adolescents 12 years and over: Seretide
Accuhaler - one inhalation b.d. of: Seretide 100 (salmeterol 50
mcg/fluticasone propionate 100 mcg) or Seretide 250 (salmeterol 50
mcg/fluticasone propionate 250 mcg) or Seretide 500 (salmeterol 50
mcg/fluticasone propionate 500 mcg), Seretide Evohaler - two puffs
b.d. of: Seretide 50 (salmeterol 25 mcg/fluticasone propionate 50
mcg) or Seretide 125 (salmeterol 25 mcg/fluticasone propionate
125mcg) or Seretide 250 (salmeterol 25 mcg/fluticasone propionate
250 mcg). Children 4-11
years: Seretide 50 Evohaler (salmeterol 25 mcg/fluticasone
propionate 50 mcg): two puffs b.d. Spacer recommended for
co-ordination. Seretide 100 Accuhaler (salmeterol 50
mcg/fluticasone propionate 100 mcg) one inhalation b.d. Regularly
review patients and reduce dose to lowest that maintains effective
symptom control. Where the control of symptoms is maintained with
the lowest strength of the combination, patients may be prescribed
an inhaled corticosteroid alone, or if a long-acting b2 agonist is
required, Seretide may be given once daily. If rapid control of
asthma in adults or adolescents with moderate persistent asthma
(defined as patients with daily symptoms, daily rescue use and
moderate to severe airflow limitation) is essential, an initial
dose of two inhalations b.d of Seretide 50 Evohaler (salmeterol 25
mcg/fluticasone propionate 50 mcg) or one inhalation b.d of
Seretide 100 Accuhaler (salmeterol 50 mcg/fluticasone propionate
100 mcg) may be considered on a short-term basis. Once control of
asthma is attained treatment should be regularly reviewed and
stepped down. Doubling the dose of all strengths of Seretide may be
considered when adult patients require additional short-term (up to
14 days) inhaled corticosteroid therapy but this causes a small
increase in b-agonist-related adverse events. COPD: one inhalation
b.d. of Seretide 500 Accuhaler (salmeterol 50mcg/fluticasone
propionate 500 mcg).
Contraindications: Hypersensitivity to the active
ingredients or to any of the excipients.
Precautions: Pulmonary tuberculosis, fungal, viral or other
infections of the airway, severe cardiovascular disorders, heart
rhythm abnormalities, diabetes mellitus, hypokalaemia and
thyrotoxicosis. Increased reporting of pneumonia and bronchitis in
patients with COPD receiving Seretide compared with placebo. If a
patient with severe COPD has experienced pneumonia, treatment with
Seretide should be re-evaluated. Paradoxical bronchospasm post
dose. Severe
unstable asthma: Warn
patients to seek medical advice if short-acting inhaled
bronchodilator use increases. Consider increased inhaled/additional
corticosteroid therapy. Acute
symptoms: Not for acute symptoms. Use short-acting inhaled
bronchodilator. Systemic
effects: Systemic effects of inhaled corticosteroids may
occur, particularly at high doses for prolonged periods, but much
less likely than with oral corticosteroids. May include Cushing's
syndrome, cushingoid features, adrenal suppression, adrenal crisis,
growth retardation in children and adolescents, decrease in bone
mineral density, cataract, glaucoma and, more rarely, a range of
psychological or behavioural effects including psychomotor
hyperactivity, sleep disorders, anxiety, depression or aggression
(particularly in children). Monitor height of children on prolonged
inhaled corticosteroid therapy. Tremor, palpitations and headache,
have been reported with b2 agonist
treatment. In asthma, therapy should be down titrated under
physician supervision to lowest effective dose and treatment should
not be abruptly stopped due to risk of exacerbation. Serious
asthma-related adverse events and exacerbations may occur during
treatment with Seretide. Patients should not be initiated on
Seretide during an exacerbation, or if they have significantly
worsening or acutely deteriorating asthma. Data from a large asthma
trial suggested patients of black African or Afro-Caribbean
ancestry were at increased risk of serious respiratory-related
events or deaths when using salmeterol. All patients should
continue treatment but seek medical advice if asthma symptoms
remain uncontrolled or worsen when initiated on Seretide or using
Seretide. In COPD cessation of therapy may also be associated with
decompensation and should be supervised by a physician.
Transfer from oral
steroids: Special care needed. Consider appropriate steroid
therapy in stressful situations.
Drug interactions: Avoid beta-blockers. Avoid concomitant
administration of ketoconazole or other potent (e.g. itraconazole,
telithromycin, ritonavir) and moderate (erythromycin) CYP3A4
inhibitors unless benefits outweigh potential risk. b2 adrenergic
blockers may weaken or antagonise the effect of salmeterol.
Potentially serious hypokalaemia may result from
2
agonist therapy. Particular caution is advised in acute
severe asthma as this effect may be potentiated by concomitant
treatment with xanthine derivatives, steroids and
diuretics.
Pregnancy and lactation: Experience limited. Balance risks
against benefits.
Side
effects: Very
Common: headache, nasopharyngitis. Common: candidiasis of the mouth and
throat, hoarseness/dysphonia, throat irritation, pneumonia,
bronchitis, hypokalaemia, sinusitis, contusions, traumatic
fractures, arthralgia, myalgia, muscle cramps. Uncommon: respiratory symptoms
(dyspnoea), anxiety, tremor, palpitations, tachycardia, angina
pectoris, atrial fibrillation, cutaneous hypersensitivity
reactions, hyperglycaemia, sleep disorders, cataract. Rare: angioedema, respiratory symptoms
(bronchospasm), anaphylactic reactions including anaphylactic
shock, Cushings syndrome, cushingoid features, adrenal suppression,
growth retardation in children and adolescents, decreased bone
mineral density, oesophageal candidiasis, behavioural changes
including psychomotor hyperactivity and irritability (predominately
in children), glaucoma, cardiac arrhythmias and paradoxical
bronchospasm. Not known:
depression or aggression (particularly in children). Paradoxical bronchospasm: substitute
alternative therapy.
Seretide Accuhaler is known as ADVAIR DISKUS in the United States.
ADVAIR DISKUS is licensed in the US for:
●
The treatment of asthma
in patients aged 4 years and older.
Long-acting
beta2-adrenergic agonists (LABA), such as salmeterol, one of the
active ingredients in ADVAIR DISKUS, increase the risk of
asthma-related death. Available data from controlled clinical
trials suggest that LABA increase the risk of asthma-related
hospitalization in pediatric and adolescent patients. Therefore,
when treating patients with asthma, physicians should only
prescribe ADVAIR DISKUS for patients not adequately controlled on a
long-term asthma control medication, such as an inhaled
corticosteroid, or whose disease severity clearly warrants
initiation of treatment with both an inhaled corticosteroid and a
LABA. Once asthma control is achieved and maintained, assess the
patient at regular intervals and step down therapy (e.g.,
discontinue ADVAIR DISKUS) if possible without loss of asthma
control and maintain the patient on a long-term asthma control
medication, such as an inhaled corticosteroid. Do not use ADVAIR
DISKUS for patients whose asthma is adequately controlled on low-
or medium-dose inhaled corticosteroids.
●
ADVAIR DISKUS is NOT
indicated for the relief of acute bronchospasm.
Full US prescribing information, including BOXED WARNING and
Medication Guide is available
at us.gsk.com or US
Prescribing Information for Advair Diskus.
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.
RELVAR®,
BREO®,
ELLIPTA®,
SERETIDE®,
ACCUHALER®,
ADVAIR®,
DISKUS®
are trademarks of the GlaxoSmithKline
group of companies.
Innoviva - Innoviva is focused on bringing
compelling new medicines to patients in areas of unmet need by
leveraging its significant expertise in the development,
commercialization and financial management of bio-pharmaceuticals.
Innoviva's portfolio is anchored by the respiratory assets
partnered with Glaxo Group Limited (GSK), including
RELVAR®/BREO®
ELLIPTA®
and
ANORO®
ELLIPTA®,
which were jointly developed by Innoviva and GSK. Under the
agreement with GSK, Innoviva is eligible to receive associated
royalty revenues from RELVAR®/BREO®
ELLIPTA®,
ANORO®
ELLIPTA®.
In addition, Innoviva retains a 15 percent economic interest in
future payments made by GSK for earlier-stage programs partnered
with Theravance Biopharma, Inc., including the closed triple
combination therapy for COPD. For more information, please visit
Innoviva's website at www.inva.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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Anna
Gibbins
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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)
208 047 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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Innoviva, Inc. enquiries:
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Investor
Relations:
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Eric
d'Esparbes
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+1
(650) 238-9605
investor.relations@inva.com
|
(Brisbane,
Calif.)
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GSK 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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Innoviva
forward-looking statements
This
press release contains certain "forward-looking" statements as that
term is defined in the Private Securities Litigation Reform Act of
1995 regarding, among other things, statements relating to goals,
plans, objectives and future events, including the development,
regulatory and commercial plans for closed triple combination
therapy and the potential benefits and mechanisms of action of
closed triple combination therapy. Innoviva intends such
forward-looking statements to be covered by the safe harbor
provisions for forward-looking statements contained in Section 21E
of the Securities Exchange Act of 1934 and the Private Securities
Litigation Reform Act of 1995. Such forward-looking statements
involve substantial risks, uncertainties and assumptions. These
statements are based on the current estimates and assumptions of
the management of Innoviva as of the date of this press release and
are subject to risks, uncertainties, changes in circumstances,
assumptions and other factors that may cause the actual results of
Innoviva to be materially different from those reflected in the
forward-looking statements. Important factors that could cause
actual results to differ materially from those indicated by such
forward-looking statements are described under the headings "Risk
Factors" and "Management's Discussion and Analysis of Financial
Condition and Results of Operations" contained in Innoviva's Annual
Report on Form 10-K for the year ended December 31, 2015 and
Quarterly Report on Form 10-Q for the quarter ended September 30,
2016, which are on file with the U.S. Securities and Exchange
Commission (SEC) and available on the SEC's website at www.sec.gov.
Additional factors may be described in those sections of Innoviva's
Annual Report on Form 10-K for the year ended December 31, 2016, to
be filed with the SEC in the first quarter of 2017.. In addition to
the risks described above and in Innoviva's other filings with the
SEC, other unknown or unpredictable factors also could affect
Innoviva's results. No forward-looking statements can be guaranteed
and actual results may differ materially from such statements.
Given these uncertainties, you should not place undue reliance on
these forward-looking statements. The information in this press
release is provided only as of the date hereof, and Innoviva
assumes no obligation to update its forward-looking statements on
account of new information, future events or otherwise, except as
required by law. (INVA-G).
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: February
23, 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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