Once-Daily Trelegy Ellipta Gains Expanded Indication in the US for the Treatment of Patients With COPD
GlaxoSmithKline plc (LSE/NYSE: GSK) and Innoviva, Inc. (NASDAQ: INVA) today announced that the US Food and Drug Administration
(FDA) has approved an expanded indication for Trelegy Ellipta (fluticasone furoate/umeclidinium/vilanterol ‘FF/UMEC/VI’), which
means Trelegy Ellipta can now be used by US physicians to treat a broader population of chronic obstructive pulmonary disease
(COPD) patients with airflow limitation or who have experienced an acute worsening of respiratory symptoms.
The new indication is for the long-term, once-daily, maintenance treatment of airflow obstruction in patients with COPD,
including chronic bronchitis and/or emphysema. It is also indicated to reduce exacerbations of COPD in patients with a history of
exacerbations. It is not indicated for relief of acute bronchospasm or for the treatment of asthma.
Dr. Hal Barron, Chief Scientific Officer and President of Research and Development, GSK, said, “Following the initial approval
of Trelegy Ellipta in September, we have analysed the data from the IMPACT study and identified additional benefits
that this important medicine offers patients with chronic obstructive pulmonary disease. We are pleased that
the robust data from the IMPACT study has enabled the expanded indication announced today and the FDA action has been
taken so swiftly. We will continue to analyse the data from the IMPACT trial and our
ongoing Trelegy Ellipta studies to demonstrate further the value of this important medicine to patients.”
The approval is based on a supplemental New Drug Application (sNDA) supported by data from the landmark InforMing the PAthway of
COPD Treatment (IMPACT) study which showed Trelegy Ellipta was superior to the inhaled corticosteroid/long-acting
beta2-adrenergic agonist (ICS/LABA), Relvar/Breo Ellipta (FF/VI), and long-acting muscarinic antagonist/long-acting
beta2-adrenergic agonist (LAMA/LABA), Anoro Ellipta (UMEC/VI), on multiple clinically important endpoints, including
reducing exacerbations and improving lung function and health related quality of life.
Dr Ted Witek, Senior Vice President and Chief Scientific Officer at Innoviva added: “Up to half of patients with COPD on
maintenance therapy will have experienced at least one exacerbation in the past 12 months, so gaining an indication that reflects
the role Trelegy Ellipta can play in reducing this risk is important. We welcome this regulatory update which will allow physicians
to offer the benefits of once-daily single inhaler triple therapy to appropriate patients with COPD.”
Trelegy Ellipta was originally approved for use in the US in September 2017 for the long-term, once-daily, maintenance treatment
of COPD patients who are receiving Breo and require additional bronchodilation or who are receiving Breo and Incruse (UMEC). A type
II variation to support an expanded label in Europe was submitted to the European Medicines Agency (EMA) in February 2018 and is
currently under review.
The boxed warning has also been removed from the Trelegy Ellipta prescribing information, in line with the recent updates to the
ICS/LABA class. Labelling changes to ICS/LABA combination medicines were implemented following a review of safety data submitted to
the FDA by three companies including GSK and approved on December 20, 2017.
About IMPACT
The regulatory update is based on the positive results of the landmark 10,355-patient InforMing the PAthway of COPD Treatment
(IMPACT) study. IMPACT is the first study to directly compare three commonly-used COPD combination treatment
classes delivered using the same dose and inhaler. It is the second of two phase 3 studies designed to investigate the efficacy and
safety of FF/UMEC/VI in a single inhaler compared to other commonly-used COPD combination treatments.2
IMPACT evaluated as its primary endpoint the annual rate of on-treatment moderate/severe exacerbations for FF/UMEC/VI
(100/62.5/25mcg) compared with FF/VI (100/25mcg) and UMEC/VI (62.5/25mcg), two once-daily dual COPD therapies from GSK’s existing
portfolio. Results from IMPACT were recently published in the New England Journal of Medicine. 3
About Trelegy Ellipta (FF/UMEC/VI)
FF/UMEC/VI is the first COPD treatment to provide a combination of three molecules in a single inhaler that is taken in a single
inhalation, once a day. It contains fluticasone furoate, an inhaled corticosteroid, umeclidinium, a long-acting muscarinic
antagonist; and vilanterol, a long-acting beta2-adrenergic agonist, delivered in GSK’s Ellipta dry powder inhaler, which is used
across the entire new portfolio of inhaled COPD medicines.
Data from across multiple clinical programmes have demonstrated the benefit of the molecules in FF/UMEC/VI both alone and in
combination, for the treatment of COPD.
FF/UMEC/VI was approved in the US in September 2017 for the long-term, once-daily, maintenance treatment of patients with COPD,
including chronic bronchitis and/or emphysema, who are on a fixed-dose combination of FF/VI for airflow obstruction and reducing
exacerbations in whom additional treatment of airflow obstruction is desired or for patients who are already receiving UMEC and a
fixed-dose combination of FF/VI.
Full US Prescribing Information, including Patient Information is available at: https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Trelegy/pdf/TRELEGY-PI-MG-IFU.PDF
FF/UMEC/VI was approved for use in Europe in November 2017 as a maintenance treatment in adult patients with moderate to severe
COPD who are not adequately treated by a combination of an inhaled corticosteroid and a long-acting beta2-agonist. The
European Summary of Product Characteristics is available at: https://www.medicines.org.uk/emc/medicine/34357
Regulatory applications for once-daily single inhaler triple therapy FF/UMEC/VI have been submitted and are undergoing
assessment in a number of other countries.
About COPD
COPD is a progressive lung disease that is thought to affect around 384 million people worldwide.4 For people living
with COPD, the inability to breathe normally can consume their daily lives and make simple activities, like walking up stairs, an
everyday struggle. Patients with COPD suffer from symptoms of breathlessness and many have a significant risk of exacerbations.
Managing these aspects of the disease drives physician treatment choice.
Long-term exposure to inhaled irritants that damage the lungs and the airways are usually the cause of COPD. Cigarette smoke,
breathing in second hand smoke, air pollution, chemical fumes or dust from the environment or workplace can all contribute to COPD.
Most people who have COPD are at least 40 years old when symptoms begin.5
Every person with COPD is different, with different needs, different challenges and different goals. Understanding this and
providing support to help meet these needs is the foundation of GSK’s work.
GSK’s commitment to respiratory disease
GSK has led the way in developing innovative medicines to advance the management of asthma and COPD for nearly 50 years. Over
the last five years we have launched six innovative medicines responding to continued unmet patient need, despite existing
therapies. This is an industry-leading portfolio in breadth, depth and innovation, developed to reach the right patients, with the
right treatment.
We remain at the cutting-edge of scientific research into respiratory medicine, working in collaboration with patients and the
scientific community to offer innovative medicines aimed at helping to treat patients’ symptoms and reduce the risk of their
disease worsening. While respiratory diseases are clinically distinct, there are important pathophysiological features that span
them, and our ambition is to have the most comprehensive portfolio of medicines to address a diverse range of respiratory diseases.
To achieve this, we are focusing on targeting the underlying disease-driving biological processes to develop medicines with
applicability across multiple respiratory diseases. This approach requires extensive bioinformatics, data analytic capabilities,
careful patient selection and stratification by phenotype in our clinical trials.
Important Safety Information (ISI)
The following ISI is based on the Highlights section of the US Prescribing Information for FF/UMEC/VI. Please consult the full
Prescribing Information for all the labelled safety information.
Trelegy Ellipta is contraindicated in patients with severe hypersensitivity to milk proteins or any of the ingredients.
LABA monotherapy increases the risk of serious asthma-related events.
Trelegy Ellipta should not be initiated in patients experiencing episodes of acutely deteriorating COPD. Do not use Trelegy
Ellipta to treat acute symptoms.
Trelegy Ellipta should not be used in combination with other medicines containing LABA because of risk of overdose.
Candida albicans infection of the mouth and pharynx has occurred in patients treated with fluticasone furoate, a component of
Trelegy Ellipta. Monitor patients periodically. Advise the patient to rinse his/her mouth with water without swallowing after
inhalation to help reduce the risk.
There is an increased risk of pneumonia in patients with COPD taking Trelegy Ellipta. Monitor patients for signs and symptoms of
pneumonia.
Patients who use corticosteroids are at risk for potential worsening of infections (e.g. existing tuberculosis; fungal,
bacterial, viral, or parasitic infections; or ocular herpes simplex). Use Trelegy Ellipta with caution in patients with these
infections. More serious or even fatal course of chickenpox or measles can occur in susceptible patients.
There is a risk of impaired adrenal function when transferring from systemic corticosteroids. Taper patients slowly from
systemic corticosteroids if transferring to Trelegy Ellipta.
Hypercorticism and adrenal suppression may occur with very high dosages or at the regular dosage of Trelegy Ellipta in
susceptible individuals. If such changes occur, consider appropriate therapy.
If paradoxical bronchospasm occurs, discontinue Trelegy Ellipta and institute alternative therapy.
Use Trelegy Ellipta with caution in patients with cardiovascular disorders because of beta-adrenergic stimulation.
Assess patients for decrease in bone mineral density initially and periodically thereafter after prescribing Trelegy
Ellipta.
Close monitoring for glaucoma and cataracts is warranted in patients taking Trelegy Ellipta. Worsening of narrow-angle glaucoma
may occur. Use with caution in patients with narrow-angle glaucoma and instruct patients to contact a healthcare provider
immediately if symptoms occur.
Worsening of urinary retention may occur in patients taking Trelegy Ellipta. Use with caution in patients with prostatic
hyperplasia or bladder-neck obstruction and instruct patients to contact a healthcare provider immediately if symptoms occur.
Use Trelegy Ellipta with caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, and ketoacidosis.
Be alert to hypokalemia and hyperglycemia in patients taking Trelegy Ellipta.
The most common adverse reactions reported for Trelegy Ellipta (incidence ≥1%) are upper respiratory tract infection, pneumonia,
bronchitis, oral candidiasis, headache, back pain, arthralgia, influenza, sinusitis, pharyngitis, rhinitis, dysgeusia,
constipation, urinary tract infection, diarrhea, gastroenteritis, oropharyngeal pain, cough, and dysphonia.
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.
Trademarks are owned by or licensed to the GSK group of companies.
Innoviva – Innoviva is focused on bringing compelling 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 ® , ANORO ® ELLIPTA ® and
TRELEGY® 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
® and ANORO ® ELLIPTA ® . In addition, Innoviva retains a 15
percent economic interest in future payments made by GSK for TRELEGY® ELLIPTA® and earlier-stage programs partnered with Theravance
Biopharma, Inc. For more information, please visit Innoviva's website at www.inva.com.
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 2017.
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, 2017, which is on file with the 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 Quarterly Report on Form 10-Q
for the quarter ended March 31, 2018, to be filed with the SEC in the second quarter of 2018. 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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References (accessed March 2018)
1. GSK data on file. RF/CPD/0003/18. Frequency of acute exacerbations of COPD among patients treated with maintenance therapy in
three observational studies.
2. Lipson DA et al. FULFIL Trial: Once-Daily Triple Therapy for Patients with Chronic Obstructive Pulmonary Disease. Am J Resp
Crit Care Med. 2017.
3. Lipson DA et al. Once-Daily Single Inhaler Triple Versus Dual Therapy in Patients with COPD. New England Journal of Medicine.
2018.
4. Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease
(GOLD) 2017. Available from: http://goldcopd.org.
5. Diagnosis of COPD. World Health Organization. Available at: http://www.who.int/respiratory/copd/diagnosis/en/
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