DUBLIN, HERTFORDSHIRE, England and PITTSBURGH, May 23,
2017 /PRNewswire/ -- Theravance Biopharma, Inc.
(NASDAQ: TBPH) ("Theravance Biopharma") and Mylan N.V. (NASDAQ,
TASE: MYL) ("Mylan") today announced the presentation of additional
efficacy and safety data from the three-month, pivotal Phase 3
studies of revefenacin (TD-4208) at the American Thoracic Society
(ATS) International Conference in Washington, D.C. Revefenacin is an
investigational long-acting muscarinic antagonist (LAMA) and a
proposed once-daily, nebulized bronchodilator in development for
the treatment of chronic obstructive pulmonary disease (COPD).
Phase 3 Pivotal Study Presentations
Researchers presented new data from the completed three-month
Phase 3 studies, which included more than 1,250 patients with
moderate to very severe COPD, in two separate presentations at the
2017 ATS meeting. The first
presentation, which focused on efficacy outcomes, demonstrated
statistically significant and clinically meaningful improvements
over placebo in trough forced expiratory volume in one second
(FEV1) and in overall treatment effect on trough
FEV1 (OTE FEV1) after 12 weeks of dosing in
each study and for each of the revefenacin doses studied (88 mcg
once daily and 175 mcg once daily). The improvements in trough
FEV1, the primary efficacy endpoint, versus placebo for
the intent-to-treat populations across both studies were 118 mL and
145 mL for 88 mcg and 175 mcg, respectively (p ≤ 0.001).
Additionally, the improvements in OTE FEV1, a key
secondary endpoint, versus placebo for the intent-to-treat
population across both studies were 112 mL and 139 mL for 88 mcg
and 175 mcg, respectively (p ≤ 0.001).
The second presentation featured safety and tolerability data
from the two completed three-month Phase 3 studies. Both doses of
revefenacin had comparable rates of adverse events to placebo, low
rates of serious adverse events, and no clinically meaningful
differences in blood parameters or electrocardiogram (ECG) data,
across all treatment groups (active and placebo). As previously
reported, the most commonly reported adverse events, across both
trials and across all treatment groups, were exacerbations, cough,
dyspnea and headache. There were no reports of blurred vision,
narrow-angle glaucoma or worsening of urinary retention. Reports of
dry mouth were <0.5% in the revefenacin treatment arms.
"These presentations build upon the topline results that we
announced last October and further confirm that revefenacin may
offer meaningful benefits to patients with moderate to very severe
COPD," said Brett Haumann,
MD, Chief Medical Officer at Theravance Biopharma. "We believe
that these results position revefenacin favorably as a potentially
key therapeutic option for COPD patients if approved, particularly
as revefenacin would represent the first once-daily nebulized
bronchodilator for COPD. We anticipate completing the ongoing Phase
3 safety trial of revefenacin in mid-2017 with the goal of filing
an NDA by the end of 2017."
Mylan President Rajiv Malik
commented, "We continue to be very pleased with the progress of the
Phase 3 revefenacin program, and are excited to have the
opportunity to showcase this important data set at ATS for the
first time. According to the GOLD Guidelines for COPD, LAMAs are a
cornerstone of therapy for moderate to severe COPD, yet there are
currently no nebulized LAMAs available. We believe this product has
the potential to help address an unmet medical need for patients.
Further, revefenacin represents a key contributor in Mylan's
pipeline of promising respiratory products, and supports the growth
of our respiratory franchise. If approved, we believe that we are
well-positioned to support the commercial success of this
product."
Revefenacin is being developed as a once-daily, nebulized
bronchodilator for the treatment of patients with COPD and will be
compatible with a range of jet nebulizers. The three-month Phase 3
pivotal studies were replicate, randomized, double-blind,
placebo-controlled, parallel-group trials designed to provide
pivotal efficacy and safety data for once-daily revefenacin over a
dosing period of 12 weeks. The replicate studies enrolled a
combined total of over 1,250 patients in the U.S. across a range of
disease severity from moderate to very severe COPD and allowed for
the concomitant use of long-acting beta agonist (LABA) and/or
long-acting beta agonist/inhaled corticosteroid (LABA/ICS) products
in a significant proportion (38%) of the studied population. Study
investigators tested two doses (88 mcg and 175 mcg) of revefenacin
inhalation solution or matched placebo administered once daily via
a standard jet nebulizer in moderate to very severe COPD
patients.
The revefenacin Phase 3 program also includes an ongoing
12-month, open-label, active comparator safety study in more than
1,050 patients, which is expected to be completed in mid-2017.
Together, the three studies enrolled approximately 2,300 patients.
Should outcomes from the safety study be supportive, Theravance
Biopharma expects to file a New Drug Application (NDA) for
revefenacin with the U.S. Food and Drug Administration (FDA) by the
end of 2017. Theravance Biopharma and its affiliates have partnered
with Mylan and its affiliates on the development and
commercialization of nebulized revefenacin products for COPD and
other respiratory diseases.
Additional Data Presentations
In a separate presentation at 2017
ATS, researchers reported baseline data on the prevalence of
COPD patients with low peak inspiratory flow rate (PIFR) who are
enrolled in the ongoing 12-month, open-label, active comparator
safety study of revefenacin. Of the total population of 1,080
patients who were enrolled in the study, 448 patients had their
PIFR measured using a commercially available, easy-to-use
instrument (InCheck®) at the time of study
randomization. Researchers categorized PIFRs of less than 40 L/min
against the resistance of the Handihaler® as "low" for
the means of this analysis based upon published research and
reference data. Presented results showed that 24% of subjects had a
low PIFR rate at the time of randomization. Analysis of patient
characteristics showed that patients with a low PIFR tended to be
female and exhibited evidence of more severe COPD, although a
proportion of patients with less severe COPD were also found to
have low PIFR.
"Patients with low PIFR may not be able to breathe in with
enough force to benefit from the use of handheld COPD devices.
There is growing evidence that these patients may have better
short-term and long-term benefits from nebulized therapy. This is
supported by a recent scientific study that reported that patients
with low PIFR, regardless of disease severity, showed statistically
significant lower COPD hospital readmission rates within both 30
and 90 days when using nebulized therapy as compared to a handheld
product following COPD exacerbation1," said Dr. Haumann.
"We believe that revefenacin could provide a unique benefit to
patients with low PIFR and are currently evaluating this in a
dedicated clinical study."
Researchers also presented results from a study highlighting the
pharmacological properties of revefenacin in isolated tissue
airways, from both rats and humans, to enable preclinical to
clinical translation of the in vivo findings in rats. Study
data demonstrated that revefenacin produced potent and persistent
anti-muscarinic activity in the airway tissues of both rats and
humans. These translational findings are consistent with clinical
data from the replicate three-month Phase 3 studies of revefenacin
demonstrating 24-hour bronchodilatory effects in COPD patients.
About Theravance Biopharma and Mylan Strategic
Collaboration
Theravance Biopharma and Mylan N.V. and their respective
affiliates have established a strategic collaboration to develop
and commercialize nebulized revefenacin products for COPD and other
respiratory diseases. Under the terms of the agreement, Theravance
Biopharma is leading the U.S. development program for the
revefenacin inhalation solution product, with all costs reimbursed
by Mylan up until the approval of the first new drug application,
after which costs will be shared. Mylan is responsible for ex-U.S.
development and commercialization. Theravance Biopharma is eligible
to receive up to $220 million in
development and sales milestone payments, as well as a
profit-sharing arrangement with Mylan on U.S. sales and
double-digit royalties on ex-U.S. sales. Additionally, Theravance
Biopharma retains worldwide rights to revefenacin delivered
through other dosage forms, such as a metered dose inhaler or dry
powder inhaler (MDI/DPI), and the rights to nebulized revefenacin
in China.
About COPD
COPD is a growing and devastating disease that is the third
leading cause of death in the U.S.2 An estimated 12.7
million American adults are diagnosed with COPD and an almost equal
number are believed to be undiagnosed.3 There were more
than 700,000 hospital discharges related to COPD in the U.S.
reported in 2010. The costs of managing COPD in the U.S. were
estimated to be nearly $50 billion in
2010, including $29.5 billion in
direct healthcare expenditures, $8
billion in indirect morbidity costs and $12.4 billion in indirect mortality
costs.3
About Revefenacin
Revefenacin (TD-4208) is a novel investigational once-daily
nebulized LAMA in Phase 3 development for the treatment of moderate
to very severe COPD. Market research by Theravance Biopharma
indicates approximately 9% of the treated COPD patients in the U.S.
use nebulizers for ongoing maintenance therapy.4 LAMAs
are a cornerstone of maintenance therapy for COPD and, if approved,
revefenacin would provide a once-daily option for COPD patients who
require, or prefer, nebulized therapy. The product's stability in
both metered dose inhaler and dry powder device formulations
suggest that this LAMA could also serve as a foundation for novel
handheld combination products.
About Theravance Biopharma
Theravance Biopharma is a diversified biopharmaceutical company
with the core purpose of creating medicines that help improve the
lives of patients suffering from serious illness.
Our pipeline of internally discovered product candidates
includes potential best-in-class medicines to address the unmet
needs of patients being treated for serious conditions primarily in
the acute care setting. VIBATIV® (telavancin), our first
commercial product, is a once-daily dual-mechanism antibiotic
approved in the U.S., Europe and
certain other countries for certain difficult-to-treat infections.
Revefenacin (TD-4208) is a long-acting muscarinic antagonist (LAMA)
being developed as a potential once-daily, nebulized treatment for
chronic obstructive pulmonary disease (COPD). Our neprilysin (NEP)
inhibitor program is designed to develop selective NEP inhibitors
for the treatment of a range of major cardiovascular and renal
diseases, including acute and chronic heart failure, hypertension
and chronic kidney diseases, such as diabetic nephropathy. Our
research efforts are focused in the areas of inflammation and
immunology, with the goal of designing medicines that provide
targeted drug delivery to tissues in the lung and gastrointestinal
tract in order to maximize patient benefit and minimize risk. The
first program to emerge from this research is designed to develop
intestinally restricted pan-Janus kinase (JAK) inhibitors for the
treatment of a range of inflammatory intestinal diseases.
In addition, we have an economic interest in future payments
that may be made by Glaxo Group Limited or one of its affiliates
(GSK) pursuant to its agreements with Innoviva, Inc. relating to
certain drug development programs, including the Closed Triple (the
combination of fluticasone furoate, umeclidinium, and vilanterol),
currently in development for the treatment of COPD and asthma.
For more information, please visit www.theravance.com.
THERAVANCE®, the Cross/Star logo, and VIBATIV® are registered
trademarks of the Theravance Biopharma group of companies.
Trademarks, trade names or service marks of other companies
appearing on this press release are the property of their
respective owners.
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, expectations and
future events. Theravance Biopharma 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 company's strategies, plans and
objectives, the company's regulatory strategies and timing of
clinical studies, the potential benefits and mechanisms of action
of the company's product and product candidates, the company's
expectations for product candidates through development, potential
regulatory approval and commercialization (including their
potential as components of combination therapies) and the company's
expectations for product sales. These statements are based on the
current estimates and assumptions of the management of Theravance
Biopharma as of the date of the press release and the conference
call and are subject to risks, uncertainties, changes in
circumstances, assumptions and other factors that may cause the
actual results of Theravance Biopharma 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 include, among
others, risks related to: delays or difficulties in commencing or
completing clinical studies, the potential that results from
clinical or non-clinical studies indicate the company's product
candidates are unsafe or ineffective (including when our product
candidates are studied in combination with other compounds),the
feasibility of undertaking future clinical trials for our product
candidates based on FDA policies and feedback, dependence on third
parties to conduct clinical studies, delays or failure to achieve
and maintain regulatory approvals for product candidates, risks of
collaborating with or relying on third parties to discover, develop
and commercialize product and product candidates, and risks
associated with establishing and maintaining sales, marketing and
distribution capabilities with appropriate technical expertise and
supporting infrastructure. Other risks affecting Theravance
Biopharma are described under the heading "Risk Factors" contained
in Theravance Biopharma's Form 10-Q filed with the Securities and
Exchange Commission (SEC) on May 9,
2017 and Theravance Biopharma's other filings with the SEC.
In addition to the risks described above and in Theravance
Biopharma's filings with the SEC, other unknown or unpredictable
factors also could affect Theravance Biopharma'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. Theravance Biopharma assumes no obligation to update
its forward-looking statements on account of new information,
future events or otherwise, except as required by law.
About Mylan
Mylan is a global pharmaceutical company committed to setting
new standards in healthcare. Working together around the world to
provide 7 billion people access to high quality medicine, we
innovate to satisfy unmet needs; make reliability and service
excellence a habit; do what's right, not what's easy; and impact
the future through passionate global leadership. We market a
growing portfolio of approximately 7,500 products around the world,
including antiretroviral therapies on which approximately 50% of
people being treated for HIV/AIDS in the developing world depend.
We market our products in more than 165 countries and territories.
We are one of the world's largest producers of active
pharmaceutical ingredients. Every member of our more than
35,000-strong workforce is dedicated to creating better health for
a better world, one person at a time. Learn more at
mylan.com.
This press release includes statements that constitute
"forward-looking statements," including with regard to revefenacin
having the potential to offer meaningful benefits to patients with
moderate to very severe COPD; revefenacin being positioned
favorably as a potentially key therapeutic option for COPD patients
if approved, particularly as revefenacin would represent the first
once-daily nebulized bronchodilator for COPD; anticipated
completion of the ongoing Phase 3 safety trial of revefenacin in
mid-2017 with the goal of filing an NDA by the end of 2017;
revefenacin having the potential to help address an unmet medical
need for patients; revefenacin representing a key contributor in
Mylan's pipeline of promising respiratory products, and supporting
the growth of Mylan's respiratory franchise; Mylan's belief that it
is well-positioned to support the commercial success of the
product; the ongoing 12-month, open-label, active comparator safety
study in more than 1,050 patients, which is expected to be
completed in mid-2017; Theravance Biopharma expecting to file a New
Drug Application (NDA) for revefenacin with the U.S. Food and Drug
Administration (FDA) by the end of 2017; the possibility that
revefenacin could provide a unique benefit to patients with low
PIFR; and the possibility that this LAMA could also serve as a
foundation for novel handheld combination products. These
statements are made pursuant to the safe harbor provisions of the
Private Securities Litigation Reform Act of 1995. Because such
statements inherently involve risks and uncertainties, actual
future results may differ materially from those expressed or
implied by such forward-looking statements. Factors that could
cause or contribute to such differences include, but are not
limited to: success of clinical trials and our and our partners'
ability to execute on new product opportunities; any regulatory,
legal or other impediments to our ability to bring our and our
partners' products to market; other risks inherent in product
development; the scope, timing, and outcome of any ongoing legal
proceedings, including government investigations, and the impact of
any such proceedings on our or our partners' business; actions and
decisions of healthcare and pharmaceutical regulators, and changes
in healthcare and pharmaceutical laws and regulations, in
the United States and abroad; the
impact of competition; strategies by competitors or other third
parties to delay or prevent product introductions; the effect of
any changes in our customer and supplier relationships and customer
purchasing patterns; any other changes in third-party
relationships; changes in the economic and financial conditions
of the businesses of Mylan; uncertainties and matters beyond
the control of management; and the other risks detailed in Mylan's
filings with the Securities and Exchange Commission. Mylan
undertakes no obligation to update these statements for revisions
or changes after the date of this release.
References
1 Loh CH, Lovings T, Ohar J. Long acting nebulized
agents decrease readmissions in patients with suboptimal peak
inspiratory flow. Chest 2016;150:925A–925A.
2American Lung Association. "Chronic Obstructive
Pulmonary Disease (COPD)"
http://www.lung.org/lung-health-and-diseases/lung-disease-lookup/copd.
3 American Lung Association. "Trends in COPD (Chronic
Bronchitis and Emphysema): Morbidity and Mortality"
http://www.lung.org/assets/documents/research/copd-trend-report.pdf.
4 TBPH market research (N = 160 physicians); Refers
to US COPD patients
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SOURCE Mylan N.V.; Theravance Biopharma, Inc.