Market Overview

Relvar Ellipta Significantly Improved Asthma Control in Salford Lung Study Patients Compared with Their Usual Care


GlaxoSmithKline plc (NYSE:GSK) and Innoviva Inc (NASDAQ:INVA)
today announced positive results from the innovative Salford Lung Study
(SLS) in asthma, carried out amongst 4,233 patients treated by their own
General Practitioner in everyday clinical practice. This open-label,
randomised study showed that significantly more asthma patients
initiated on treatment with Relvar Ellipta 100/25mcg or 200/25mcg
(fluticasone furoate ‘FF'/vilanterol ‘VI' or ‘FF/VI') achieved an
improvement in their asthma control compared with patients who continued
to take their usual care medicines. Usual care treatment included
inhaled corticosteroids (ICS) administered as monotherapy or as ICS/LABA
(Long Acting Beta Agonist) combinations.

For the primary effectiveness analysis, at 24 weeks a significantly
higher percentage of patients with uncontrolled asthma and initiated on
treatment with FF/VI achieved better control of their asthma (71%)
measured by the Asthma Control Test (ACT), compared with patients
continuing usual care treatment (56%), (Odds ratio 2.00, 95% CI 1.70,
2.34; p<0.001). Improvement was defined as an ACT total score ≥20 or an
increase from baseline of ≥3. Statistically significant findings were
also seen at 12, 40 and 52 weeks.

Lead Investigator, Ashley Woodcock, Professor of Respiratory Medicine
and Clinical Director for Respiratory Medicine, University Hospital of
South Manchester and University of Manchester said: "I am really excited
to see the results from SLS asthma. Asthma control continues to be a
real challenge for patients and the healthcare community. Poor control
can have a major impact on the lives of asthma patients. The
effectiveness of different treatments on asthma control is difficult to
investigate in a traditional double-blind randomised control trial,
where the study design and intrusive monitoring can influence the
behaviour of patients. In SLS, patient relevant outcomes are the major
endpoints. GSK should be congratulated for running this unique study,
designed to understand how asthma medicines work in everyday clinical

In the study for the intent-to-treat (ITT) population, the incidence of
serious adverse events (SAE) was the same in both arms (FF/VI 13% and
usual care 13%). Pneumonia was a safety endpoint of special interest and
a regulatory post-authorisation requirement of the European Medicines
Agency (EMA). A novel aspect of the study design was that it allowed
patient's treatment to be modified throughout the study. Therefore two
assessments relating to pneumonia have been performed, one based on the
arm to which patients were randomised, the second based upon the
treatment to which patients were exposed at the time of the event.
Serious adverse events of pneumonia by randomised group were reported by
39 patients (FF/VI arm 23, 1%; usual care arm 16, <1%). These patients
had 42 events and based on a pre-planned analysis non-inferiority of
FF/VI to usual care was not confirmed. When these events were summarised
according to the actual treatment patients were taking at the time of
the event, 21 events were recorded for FF/VI and 21 events for usual

Eric Dube, Senior Vice President and Head, Global Respiratory Franchise
GSK, said: "Despite medical advances, more than half of patients with
asthma continue to experience poor control and significant symptoms. The
primary endpoint of this study showed that patients initiated with
Relvar Ellipta treatment had twice the odds of achieving an improvement
in asthma control compared with patients continuing usual care in this
study in everyday clinical practice. This study has been a tremendous
partnership effort between healthcare professionals, patients, academics
and GSK and we would like to thank everyone who has helped to make this
unique study possible."

Michael W. Aguiar, President and Chief Executive Officer of Innoviva
said: "We are delighted to see the positive results from a second SLS
study with Relvar Ellipta, the first being in chronic obstructive
pulmonary disease. Asthma control remains a significant unmet medical
need in the daily lives for many patients. We believe that this positive
real world data successfully builds upon the previous clinical data to
provide strong evidence of the benefits of Relvar Ellipta for the
treatment of asthma."

These data will be presented in future publications and will be made
available on

Study Design

The Salford Lung Study is a Phase III multi-centre, open label
randomised controlled trial (RCT). The objective of this study was to
compare the effectiveness and safety profile of initiating treatment
with FF/VI with usual asthma maintenance therapy over a 52 week period.
All suitable patients with asthma at 74 primary care sites in and around
Salford and South Manchester, UK, were identified from practice
databases and invited to participate in the study by their own GP. The
primary endpoint of the study was measured at week 24 in the primary
effectiveness analysis population.

In total, 4,233 patients with asthma who were taking an inhaled
corticosteroid (ICS) with or without a long acting beta2-agonist
(LABA) were randomised to receive either FF/VI or to continue on their
existing asthma maintenance therapy (usual care).

Usual care was prescribed by the patients GP and included ICS either
alone or in a combination with a LABA. In the usual care arm 36% of
patients were on an ICS alone and 64% were on an ICS/LABA combination at
the time of commencing study medication.

The Salford Lung Study had minimal exclusion criteria and involved a
broad demographic of patients. At baseline patients had a mean age of
49.8 (min 18 years) and were split by gender (males vs. female 41/59%).
To enrol in the study, patients were required to have a GP diagnosis of
asthma as their primary respiratory disease and be receiving maintenance
therapy with an ICS with or without LABA for at least 4 weeks prior to
visit 2. At baseline 72% of patients had uncontrolled asthma with an ACT
total score of 5 to 19.

Patients were followed for a period of 52 weeks in a normal clinical
practice setting using their electronic medical record (EMR), linking
primary care, secondary care and pharmacy data to collect study data.
Throughout the duration of the study physicians were allowed to modify
or switch treatment at any point as this would happen in normal clinical
practice, the only exception being a switch from usual care to FF/VI.

At weeks 12, 24, and 40 patients were telephoned to enquire about
whether they had experienced any serious adverse events or non-serious
adverse drug reactions. On these telephone calls patients were asked to
provide responses to the ACT. At month 12 a face to face visit was
carried out. The Standardised Asthma Quality of Life Questionnaire
(AQLQ[S]) was also conducted at week 24 and week 52 by telephone.

The study team was able to monitor all hospital admissions, outpatient
and emergency department visits, as well as data from primary care
(including all healthcare contacts, out-of-hours activity and
prescriptions of antibiotics or oral steroids) via the electronic health

The Intent-to-Treat (ITT) population is defined as all patients who have
been randomised and received at least one prescription of study
medication (e.g., FF/VI or usual asthma maintenance therapy). The
primary effectiveness analysis (PEA) population is defined as all ITT
patients who have an ACT total score of < 20 at baseline (Randomisation

The odds ratio expressed in the results is calculated as the ratio of
the odds of achieving better asthma control as a patient initiated with
Relvar Ellipta and the odds of achieving better asthma control as a
patient continuing on usual care. This value is adjusted for any
imbalances between the treatment arms in certain key characteristics.

The study design protocol paper can be found on

The Asthma Control Test (ACT)

The ACT is a well recognised instrument that is used globally in asthma
treatment guidelines to assess asthma control. It is self-administered
utilising 5 questions to assess asthma control during the past 4 weeks
on a 5-point categorical scale (1 to 5). By answering all five
questions, a patient with asthma can obtain a score that may range
between 5 and 25, with higher scores indicating better control.

An ACT total score of 5 to 19 suggests that a patient's asthma is poorly
or not well controlled. A score of 20 to 25 suggests that a patient's
asthma is likely to be well controlled. The total score is calculated as
the sum of the scores from all 5 questions, provided all scores are
non-missing; if any individual scores are missing then the overall score
will be set to missing. A change of 3 points is clinically meaningful
for the patient.

About the Study

The Salford Lung Study is intended to enable healthcare professionals
and decision makers to more fully assess the potential value of FF/VI by
providing data collected in a normal clinical practice setting which is
representative of how healthcare professionals and patients may use the
medicine in everyday life. It will add to the existing data set from
double blind randomised clinical trials (RCTs) for the medicine which,
while critical to establishing the safety and efficacy of a medicine,
are conducted in a highly controlled environment and enrol a more highly
selected patient population than would be expected in everyday clinical

The study is made possible through a unique collaboration between GSK,
North West e-Health (NWEH), The University of Manchester, Salford Royal
NHS Foundation Trust, University Hospital of South Manchester (UHSM),
NHS Salford and GPs and community pharmacists in Salford, Trafford and
South Manchester.

The Salford Lung Study in COPD reported findings in May 2016. This is
the second of the two Salford Lung Studies to report.

About asthma

Asthma is a chronic lung disease that inflames and narrows the airways.
Asthma affects 358 million people worldwide.

The causes of asthma are not completely understood but likely involve an
interaction between a person's genetic make-up and the environment.

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

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

An increase in the incidence of pneumonia has been observed in patients
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

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.

    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 or US
Prescribing Information for Breo Ellipta

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®
which were jointly developed by Innoviva and GSK. Under the agreement
with GSK, Innoviva is eligible to receive associated royalty revenues
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

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

ANORO, BREO, RELVAR and ELLIPTA are trademarks of the GlaxoSmithKline
group of companies.

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.

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. 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, 2016, which is on
file with the U.S. Securities and Exchange Commission (SEC) and
available on the SEC's website at
Additional factors may be described in those sections of Innoviva's
Quarterly Report on Form 10-Q for the quarter ended March 31, 2017, to
be filed with the SEC in the second 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).

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