GSK and Theravance Announce Positive Results From Pivotal Phase III Study for
Fluticasone Furoate/Vilanterol in Asthma
Study Meets Primary Efficacy Endpoint
LONDON, UNITED KINGDOM and SOUTH SAN FRANCISCO, CA -- (Marketwired)
-- 12/06/13 -- GlaxoSmithKline (GSK) and Theravance, Inc. (NASDAQ:
THRX) today announced positive results from a phase III efficacy and
safety study of fluticasone furoate "FF"/vilanterol "VI" designed to
support a potential filing for an asthma indication for adults in the
For the pre-specified primary endpoint of 0-24 hour weighted mean
forced expiratory volume in one second (FEV1), FF/VI 100/25mcg
demonstrated a statistically significant improvement in lung function
compared with FF 100mcg (108ml, 95% CI 45, 171 p < 0.001) at the end
of the 12 week treatment period. In patients receiving FF/VI
200/25mcg an additional improvement of 24ml (95% CI -37, 86) was
observed when compared with FF/VI 100/25mcg.
While FF/VI is approved in the US for the maintenance treatment of
airflow obstruction in patients with chronic obstructive pulmonary
disease (COPD) and to reduce exacerbations of COPD in patients with a
history of exacerbations, FF/VI is not an FDA-approved treatment for
These results will inform GSK's discussions with the FDA on the
regulatory requirements of an asthma indication for FF/VI in the US.
The most common reported side effects across all treatment arms
included headache, nasopharyngitis, upper respiratory tract infection
and influenza. The incidences of any on-treatment serious adverse
events across all treatment arms were similar (FF 100mcg < 1%, FF/VI
100/25mcg 1%, FF/VI 200/25mcg < 1%).
Dave Allen, Head, Respiratory Therapy Area Unit, R&D said, "We are
pleased to see the results delivered by FF/VI in the treatment of
asthma. We have undertaken a large and comprehensive clinical
programme providing data on the efficacy and safety profile for FF/VI
in asthma. With these additional data we will consider our next steps
in relation to an asthma filing in the US."
"There is an ongoing unmet medical need among patients with asthma,"
said Rick E Winningham, Chief Executive Officer of Theravance. "This
is an important outcome for FF/VI and we will continue working with
GSK to determine how we can make this potential treatment available
to appropriate patients who could benefit from a new asthma
About the study design
The study is a 12 week, double-blind, parallel group, multicentre
study to assess the efficacy and safety of FF/VI 200/25mcg inhalation
powder, FF/VI 100/25mcg inhalation powder and FF 100mcg inhalation
powder, evaluating 990 patients with moderate to severe persistent
asthma. Patients were randomised to one of the three treatments taken
once-daily in the evening. The primary endpoint was weighted mean
serial FEV1 at the end of the 12 week treatment period. The primary
comparison was FF/VI 100/25mcg versus FF 100mcg.
This medicine comprises the ICS fluticasone furoate (FF) and the
long-acting beta2 agonist (LABA) vilanterol (VI), as FF/VI and is
administered via a dry powder inhaler (DPI) called Ellipta(R).
FF/VI 100/25mcg was approved in May 2013 by the US Food and Drug
Administration (FDA) in the US under brand name BREO(R) ELLIPTA(R) as
an inhaled long-term, once-daily maintenance treatment of airflow
obstruction in patients with chronic obstructive pulmonary disease
(COPD), including chronic bronchitis and / or emphysema. It is also
indicated to reduce exacerbations of COPD in patients with a history
Breo Ellipta is not approved or licensed in the US for the relief of
acute bronchospasm or the treatment of asthma. For full US
prescribing information, including BOXED WARNING and Medication Guide
please visit us.gsk.com or US Prescribing Information Breo Ellipta.
Other FF/VI Regulatory Activity
FF/VI 100/25 mcg was approved for the treatment of COPD by Health
Canada in July 2013 under the trade name Breo Ellipta. FF/VI is not
indicated for the relief of acute bronchospasm or the treatment of
asthma in Canada. In September 2013, the Japanese Ministry of Health,
Labour and Welfare (MHLW) approved FF/VI 100/25mcg and 200/25mcg for
the treatment of bronchial asthma under the trade name Relvar(R)
Ellipta(R). In October 2013 the Mexican regulatory authority approved
Relvar Ellipta 100/25mcg and 200/25mcg for the treatment of COPD and
asthma. On 18th November the European Union approved FF/VI 100/25mcg
and 200/25mcg under the trade name Relvar Ellipta for the following
Asthma: the regular treatment of asthma in adults and adolescents
aged 12 years and older where use of a combination medicinal product
(long-acting beta2-agonist and inhaled corticosteroid) is
-- patients not adequately controlled with inhaled corticosteroids and
'as needed' inhaled short-acting beta2-agonists
COPD: the symptomatic treatment of adults with chronic obstructive
pulmonary disease (COPD) with a FEV1 < 70% predicted normal
(post-bronchodilator) with an exacerbation history despite regular
FF/VI is not approved or licensed anywhere outside of the US, Canada,
Japan, Mexico and the European Union.
Relvar(R), Breo(R) and Ellipta(R) are trademarks of the
GlaxoSmithKline group of companies. The use of the brand name Relvar
is not approved by any regulatory authorities outside of Japan,
Mexico and the European Union.
Important Safety Information (ISI)
The following ISI is based on the Highlights section of the U.S.
Prescribing Information for Breo Ellipta for the maintenance
treatment of airflow obstruction in patients with COPD and to reduce
exacerbations of COPD in patients with a history of exacerbations.
Please consult the full Prescribing Information for all the labeled
safety information for Breo Ellipta.
Long-acting beta2-adrenergic agonists (LABAs), such as vilanterol,
one of the active ingredients in Breo Ellipta, increase the risk of
asthma-related death. A placebo-controlled trial with another LABA
(salmeterol) showed an increase in asthma-related deaths in subjects
receiving salmeterol. This finding with salmeterol is considered a
class effect of all LABAs, including vilanterol. The safety and
efficacy of Breo Ellipta in patients with asthma have not been
established. Breo Ellipta is not indicated for the treatment of
Breo Ellipta is contraindicated in patients with severe
hypersensitivity to milk proteins or who have demonstrated
hypersensitivity to either fluticasone furoate, vilanterol, or any of
Breo Ellipta should not be initiated in patients during rapidly
deteriorating or potentially life-threatening episodes of COPD, or as
rescue therapy for the treatment of acute episodes of bronchospasm.
Acute symptoms should be treated with an inhaled, short-acting
Breo Ellipta should not be used more often than recommended, at
higher doses than recommended, or in conjunction with other
medications containing LABAs, as an overdose may result.
Oropharyngeal candidiasis has occurred in patients treated with Breo
Ellipta. Patients should rinse their mouth with water without
swallowing after inhalation to help reduce this risk.
An increase in the incidence of pneumonia has been observed in
subjects with COPD receiving the fluticasone furoate/vilanterol
combination, including Breo Ellipta100 mcg/25 mcg, in clinical
trials. There was also an increased incidence of pneumonias resulting
in hospitalization. In some incidences these pneumonia events were
Patients who use corticosteroids are at risk for potential worsening
of existing tuberculosis; fungal, bacterial, viral, or parasitic
infections; or ocular herpes simplex. A more serious or even fatal
course of chickenpox or measles may occur in susceptible patients.
Particular care is needed for patients who have been transferred from
systemically active corticosteroids to inhaled corticosteroids
because deaths due to adrenal insufficiency have occurred in patients
with asthma during and after transfer from systemic corticosteroids
to less systemically available inhaled corticosteroids.
Hypercorticism and adrenal suppression may occur with very high
dosages or at the regular dosage of inhaled corticosteroids in
Caution should be exercised when considering the coadministration of
Breo Ellipta with long-term ketoconazole and other known strong
CYP3A4 inhibitors because increased systemic corticosteroid and
cardiovascular adverse effects may occur.
As with other inhaled medicines, Breo Ellipta can produce paradoxical
bronchospasm which may be life-threatening. Vilanterol, the LABA in
Breo Ellipta, can produce clinically significant cardiovascular
effects in some patients as measured by increases in pulse rate,
systolic or diastolic blood pressure, and also cardiac arrhythmias.
Decreases in bone mineral density have been observed with long-term
administration of products containing inhaled corticosteroids, as
have glaucoma, increased intraocular pressure, and cataracts.
Breo Ellipta should be used with caution in patients with convulsive
disorders, thyrotoxicosis, diabetes mellitus, ketoacidosis, and in
patients who are unusually responsive to sympathomimetic amines.
Beta-adrenergic agonist medicines may produce significant hypokalemia
in some patients. Beta-adrenergic agonist medicines may produce
transient hyperglycemia in some patients.
The most common adverse reactions ( ≥ 3% and more common than
in placebo) reported in two 6-month clinical trials with Breo Ellipta
(and placebo) were nasopharyngitis, 9% (8%); upper respiratory tract
infection, 7% (3%); headache, 7% (5%); and oral candidiasis, 5% (2%).
In addition to the events reported in the 6-month studies, adverse
reactions occurring in ≥ 3% of the subjects treated with Breo
Ellipta in two 1-year studies included COPD, back pain, pneumonia,
bronchitis, sinusitis, cough, oropharyngeal pain, arthralgia,
hypertension, influenza, pharyngitis, diarrhea, peripheral edema, and
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.
Theravance -- is a biopharmaceutical company with a pipeline of
internally discovered product candidates and strategic collaborations
with pharmaceutical companies. Theravance is focused on the
discovery, development and commercialization of small molecule
medicines across a number of therapeutic areas including respiratory
disease, bacterial infections, and central nervous system (CNS)/pain.
Theravance's key programmes include: RELVAR(R) ELLIPTA(R) or BREO(R)
ELLIPTA(R) (FF/VI), ANORO(TM) ELLIPTA(TM) (UMEC/VI) and MABA
(Bifunctional Muscarinic Antagonist-Beta2 Agonist), GSK961081, each
partnered with GlaxoSmithKline plc, and its oral Peripheral Mu Opioid
Receptor Antagonist programme. By leveraging its proprietary insight
of multivalency to drug discovery, Theravance is pursuing a
best-in-class strategy designed to discover superior medicines in
areas of significant unmet medical need. For more information, please
visit Theravance's web site at www.theravance.com
THERAVANCE(R), the Theravance logo, and MEDICINES THAT MAKE A
DIFFERENCE(R) are registered trademarks of Theravance, Inc.
Cautionary statement regarding forward-looking statements
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. Factors that may affect GSK' s
operations are described under Item 3.D 'Risk factors' in the
company's Annual Report on Form 20-F for 2012.
Theravance 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. Theravance 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.
Examples of such statements include statements relating to the status
and timing of clinical studies, data analysis and communication of
results, statements regarding the potential benefits and mechanisms
of action of drug candidates, statements concerning the timing of
seeking regulatory approval of our product candidates, statements
concerning the enabling capabilities of Theravance's approach to drug
discovery and its proprietary insights and statements concerning
expectations for product candidates through development and
commercialization and projections of revenue, expenses and other
financial items. These statements are based on the current estimates
and assumptions of the management of Theravance 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 Theravance to be materially different from those
reflected in its forward-looking statements. Important factors that
could cause actual results to differ materially from those indicated
by such forward-looking statements include, among others, risks
related to delays or difficulties in commencing or completing
clinical studies, the potential that results of clinical or
non-clinical studies indicate product candidates are unsafe or
ineffective, our dependence on third parties in the conduct of our
clinical studies, delays or failure to achieve regulatory approvals
for product candidates, risks of relying on third-party manufacturers
for the supply of our product and product candidates and risks of
collaborating with third parties to develop and commercialize
products. These and other risks are described in greater detail under
the heading "Risk Factors" contained in Theravance's Quarterly Report
on Form 10-Q filed with the Securities and Exchange Commission (SEC)
on November 1, 2013 and the risks discussed in our other periodic
filings with the SEC. Given these uncertainties, you should not place
undue reliance on these forward-looking statements. Theravance
assumes no obligation to update its forward-looking statements.
UK Media enquiries:
+44 (0) 20 8047 5502
+44 (0) 20 8047 5502
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+44 (0) 20 8047 5502
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Theravance, Inc. enquiries:
Michael W. Aguiar
+1 650 808 4100
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