DUBLIN, Ireland, HERTFORDSHIRE, England and PITTSBURGH, Nov. 1,
2017 /PRNewswire/ -- Theravance Biopharma, Inc.
(NASDAQ: TBPH) ("Theravance Biopharma") and Mylan N.V. (NASDAQ,
TASE: MYL) ("Mylan") today announced the presentation of additional
positive efficacy data from the three-month, pivotal Phase 3
studies of revefenacin (TD-4208) at the 2017 CHEST annual meeting
in Toronto, Ontario. 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).
James F. Donohue, MD, Professor of
Medicine, Pulmonary Diseases and Critical Care Medicine at the
University of North Carolina at Chapel
Hill, 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.
24-Hour Serial Spirometry Subgroup
The first presentation highlighted prespecified exploratory
efficacy outcomes for the 264-patient subgroup that underwent
24-hour serial spirometry following the last dose of revefenacin on
day 84 in the replicate Phase 3 studies (0126 and 0127). Results
demonstrated statistically significant and clinically meaningful
improvements for revefenacin over placebo in trough forced
expiratory volume in one second (FEV1) at all time
points measured in each study over 24 hours post-dose.1
The improvements in trough FEV1 versus placebo (0-24 h)
were 111-185 mL and 154-269 mL for 88 mcg and 175 mcg, respectively
(p < 0.01).
St. George's Respiratory Questionnaire (SGRQ) and COPD
Assessment Test (CAT)
An additional presentation on the Phase 3 studies reported
results from a prespecified secondary analysis which measured
changes in patient health status using the St. George's Respiratory
Questionnaire (SGRQ) and COPD Assessment Test (CAT). In the first
Phase 3 trial (Study 0126), researchers reported clinically
meaningful improvements in SGRQ for revefenacin as compared to
placebo in both the responder and total score analyses. Treatment
with both doses of revefenacin led to statistically significant
improvements in total CAT scores (p ≤ 0.001), as well as the
percentage of patients who experienced clinically meaningful
improvements in total CAT score (p ≤ 0.05), as compared to
placebo.
In the second Phase 3 (Study 0127), improvements in SGRQ in both
the responder and total score analyses were similar for both
revefenacin doses. However, due to a greater than expected placebo
response in this study, only the change from baseline analysis for
subjects receiving 175 mcg reached statistical significance over
placebo. Treatment with 175 mcg of revefenacin led to statistically
significant improvements in total CAT scores (p < 0.05), as well
as an increase in the percentage of patients who experienced
clinically meaningful improvements in total CAT score (p ≤ 0.05),
as compared to placebo. While the 88 mcg dose of revefenacin also
led to improvements in total CAT scores and an increase in the
percentage of patients who experienced clinically meaningful
improvements in total CAT score as compared to placebo, these
results did not reach statistical significance due to the greater
than expected placebo response in this study.
"These latest data sets from our replicate Phase 3 efficacy
studies of revefenacin provide important additional detail and
context around the therapeutic potential of this drug for COPD
patients. We are particularly pleased to see that the statistically
significant improvements in FEV1 demonstrated with
revefenacin as compared to placebo in the complete Phase 3 patient
population were consistent with the results seen in the 24-hour
serial spirometry study subgroup," said Brett Haumann, MD, Chief Medical Officer at
Theravance Biopharma. "It is also encouraging to have collected
data from these pivotal efficacy studies that show improvements
in SGRQ and CAT as compared to placebo for these patients. We
remain on track to submit an NDA for revefenacin the fourth quarter
of 2017, as we work diligently to bring the first once-daily
nebulized bronchodilator to patients with COPD."
Mylan President Rajiv Malik
commented, "We are very pleased with the progress of our Phase 3
data program in partnership with Theravance Biopharma. These new
results, combined with efficacy and safety studies presented
earlier this year, give us positive momentum as we prepare our new
drug application for revefenacin."
Theravance Biopharma and Mylan previously reported positive
results from two pivotal Phase 3 efficacy studies of revefenacin,
which demonstrated statistically significant and clinically
meaningful improvements for revefenacin as compared to placebo in
trough FEV1 and in overall treatment effect on trough
FEV1 (OTE FEV1) after 12 weeks of dosing.
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. Additionally, the
companies have previously announced positive results from a
12-month Phase 3 safety study in 1,055 patients with COPD, which
did not identify new safety issues. Rates of adverse events (AEs)
and serious adverse events (SAEs) in the study were low and
comparable to those seen in the standard of care treatment arm. The
data from these studies will support the submission of the new drug
application (NDA) for revefenacin with the U.S. Food and Drug
Administration (FDA), anticipated in the fourth quarter 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. The companies are developing revefenacin as a once-daily,
nebulized bronchodilator for the treatment of patients with COPD
that will be compatible with a range of jet nebulizers.
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 US development program for the revefenacin
inhalation solution product, with all costs related to the
registrational program reimbursed by Mylan up until the approval of
the first new drug application, after which costs will be shared.
Mylan is responsible for ex-US 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 US
sales and double-digit royalties on ex-US 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.3There 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 has the potential to be a best-in-class once-daily
single-agent product 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 intestinal 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 Trelegy Ellipta (the
combination of fluticasone furoate, umeclidinium, and vilanterol in
a single ELLIPTA® inhaler, previously referred to as the
Closed Triple), currently approved in the US for the treatment of
appropriate COPD patients and in development for the treatment of
COPD in several other countries. The product is also currently in
development for the treatment of 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 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 August 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 offer a growing
portfolio of more than 7,500 marketed 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 the outcome
of clinical trials; that Theravance Biopharma and Mylan remain on
track to submit an NDA for revefenacin the fourth quarter of 2017;
that these new results, combined with efficacy and safety studies
presented earlier this year, give Theravance Biopharma and Mylan
positive momentum as they prepare an NDA for revefenacin; that the
data from these studies will support the submission of the NDA for
revefenacin with the FDA, anticipated in the fourth quarter of
2017; that, if approved, revefenacin has the potential to be a
best-in-class once-daily single-agent product for COPD patients who
require, or prefer, nebulized therapy; and that 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. 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 or our partners'
ability to execute on new product opportunities; any regulatory,
legal or other impediments to our or our partners' ability to bring
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' businesses; 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 or our partners' 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 or its partners;
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 "Clinically meaningful" is defined by industry
established Minimal Clinically Important Difference (MCID) for lung
function (100 ml improvement in FEV1), SGRQ (change from baseline
of -4), CAT (change from baseline of -2).
2American Lung Association. "Chronic Obstructive
Pulmonary Disease (COPD)"
http://www.lung.org/lung-health-and-diseases/lung-disease-lookup/copd.
Accessed on September 29, 2016.
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.
Accessed on September 29, 2016.
4 TBPH market research (N = 160 physicians); Refers
to US COPD patients
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SOURCE Mylan N.V.