DUBLIN and HERTFORDSHIRE, England and PITTSBURGH, May 20,
2019 /PRNewswire/ -- Theravance Biopharma, Inc.
(NASDAQ: TBPH) ("Theravance Biopharma") and Mylan
N.V. (NASDAQ: MYL) ("Mylan") today announced the presentation
of data from its pivotal Phase 3 efficacy studies and a 52-week
safety study at the 2019 American Thoracic Society (ATS)
International Conference in Dallas,
Texas.
YUPELRI® (revefenacin) inhalation
solution, a long-acting muscarinic antagonist (LAMA), is the first
and only once-daily, nebulized bronchodilator approved for the
maintenance treatment of chronic obstructive pulmonary disease
(COPD) in the U.S.
Safety and Efficacy in Concomitant LABA or ICS/LABA Treatment
COPD Patient Subgroup
Researchers presented a subgroup analysis of data from the
revefenacin Phase 3 program of patients treated concurrently with
long-acting beta agonists (LABA) either with or without inhaled
corticosteroids (ICS). A prespecified subgroup analysis was
conducted on pooled data from two 12-week replicate
placebo-controlled trials (n=812). Separately, exploratory endpoint
data from a 52-week randomized, tiotropium-controlled safety trial
were analyzed (n=670). Overall, an average of 43% of patients
across the three studies were using concurrent LABA or LABA/ICS
combination therapy. This subgroup had more severe disease at
baseline. The results suggest the use of YUPELRI with LABA or
ICS/LABA may provide additional COPD symptom control particularly
in patients with more severe disease, though additional studies are
needed to confirm any such benefit. In the analysis of the pooled
data (studies 126 and 127), the once daily nebulized treatment
with revefenacin produced greater improvements from baseline
compared with placebo (p <0.0001) in day 85 trough
FEV1 among the non-LABA and LABA
subgroups. Additionally, a clinically significant improvement
of an approximately 100-mL increase in trough
FEV1 was sustained for 12 weeks for those treated
with revefenacin in both the LABA and non-LABA subgroups.
YUPELRI is a long-term maintenance therapy and should not be
initiated in patients during acutely deteriorating or potentially
life-threatening episodes of COPD, use with caution in patients
with narrow-angle glaucoma, and worsening of urinary retention may
occur. The most common adverse events in clinical trials included
cough, nasopharyngitis, upper respiratory infection, headache and
back pain.
"These findings add to the growing body of evidence that YUPELRI
may offer meaningful benefits to a broad range of COPD patients,
including those with more severe disease," said Sanjay Sethi, M.D., professor and chief of
pulmonary, critical care and sleep medicine at the University of
Buffalo's Jacobs School of Medicine & Biomedical Sciences and
lead author of the study. "As these COPD patients often require
combination treatment with both a LAMA and a LABA to manage their
disease, these data provide additional information for healthcare
providers to consider when treating their COPD patients."
Brett Haumann, M.D., chief
medical officer at Theravance Biopharma commented, "These analyses
provide further information regarding YUPELRI, which may be
relevant to the treatment of patients with COPD, including those on
the severe end of the disease spectrum. We believe this provides
additional valuable information on the benefits that YUPELRI can
offer to patients, particularly for those battling more severe
COPD."
Walt Owens, Mylan's head of
global biologics and respiratory science and operations, commented,
"These data demonstrate our ongoing commitment to address important
unmet needs for patients living with COPD through scientific
advancement following FDA approval of YUPELRI. We are very pleased
with the continued YUPELRI clinical development program and are
excited to have the opportunity to highlight these findings at
ATS."
The companies also presented the following two posters at ATS
that add to the scientific understanding and potential clinical
significance of peak inspiratory flow rate (PIFR) measurements in
patients with COPD:
Technical Peak Inspiratory Flow Rate (PIFR) Measurement
PIFR may be an important measurement in deciding whether COPD
patients are able to gain full benefit from their handheld inhalers
or whether they would be better suited to treatment with a
nebulized product. Researchers proposed a method for measuring PIFR
in clinical trials that optimizes the repeatability of the
measurements and also defines a model to characterize the
relationship between PIFR measured using different resistances –
the resistance in the DISKUS® device compared with the
resistance in the HandiHaler® device. Based on an
analysis of data from COPD patients with suboptimal PIFR,
researchers suggest that at least three measures of PIFR using the
In-Check DIAL device are taken until the two highest measurements
meet the repeatability limit for the resistance used (10 L/min
against PIFRD and 5 L/min against PIFRHH).
Researchers propose using the resistance of the dry powder inhaler
(DPI) that the patient is using for treatment at the time when
measuring PIFR.
Suboptimal PIFR Associated with Greater Dyspnea
Baseline PIFR to DISKUS® resistance
(PIFRD) and severity of dyspnea – the medical term for
shortness of breath – were analyzed from two clinical studies.
Researchers found that patients with suboptimal PIFRD
(<60 L/min) had more severe dyspnea than patients with similar
obstruction and optimal PIFRD (≥60 L/min). According to
the researchers, the differences in dyspnea observed may represent
the effect of inspiratory limitation seen in those with suboptimal
PIFRD on their respiratory muscle function, lung
hyperinflation or air trapping.
YUPELRI was approved in November
2018 based on data from two replicate pivotal Phase 3
efficacy studies which demonstrated statistically significant and
clinically meaningful improvements as compared to placebo in trough
FEV1 and in overall treatment effect on trough
FEV1 (OTE FEV1) after 12 weeks of
dosing.1 YUPELRI had comparable rates of AEs
to placebo, low rates of serious adverse events (SAEs), and no
clinically meaningful differences in blood parameters or
electrocardiogram (ECG) data, across all treatment groups (active
and placebo). YUPELRI should not be used in acutely deteriorating
COPD or to treat acute symptoms. YUPELRI use should be discontinued
if paradoxical bronchospasm occurs. As previously reported,
the most commonly reported adverse events, across both trials and
across all treatment groups, were cough, nasopharyngitis, upper
respiratory tract infection, headache, and back pain. Additionally,
the companies completed a 12-month Phase 3 open-label safety study
versus tiotropium in which no new safety issues were identified.
Rates of AEs and SAEs in the study were low and comparable to those
seen in the tiotropium treatment arm.
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. YUPELRI is a once-daily, nebulized bronchodilator for the
treatment of patients with COPD and is compatible with any standard
jet nebulizer.
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 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-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 Nearly 15.7 million Americans (6.4%) report
that they have been diagnosed with COPD and more 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 YUPELRI
YUPELRI®
(revefenacin) inhalation solution is a once-daily nebulized LAMA
approved for the maintenance treatment of COPD in the U.S. 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 YUPELRI is positioned as a
first-in-class once-daily single-agent bronchodilator product for
COPD patients who require, or prefer, nebulized therapy. YUPELRI'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.
Important Safety Information
YUPELRI is
contraindicated in patients with hypersensitivity to revefenacin or
any component of this product.
YUPELRI should not be initiated in patients during acutely
deteriorating or potentially life-threatening episodes of COPD, or
for the relief of acute symptoms, i.e., as rescue therapy for the
treatment of acute episodes of bronchospasm. Acute symptoms should
be treated with an inhaled short-acting
beta2-agonist.
As with other inhaled medicines, YUPELRI can produce paradoxical
bronchospasm that may be life-threatening. If paradoxical
bronchospasm occurs following dosing with YUPELRI, it should be
treated immediately with an inhaled, short-acting bronchodilator.
YUPELRI should be discontinued immediately and alternative therapy
should be instituted.
YUPELRI should be used with caution in patients with
narrow-angle glaucoma. Patients should be instructed to immediately
consult their healthcare provider if they develop any signs and
symptoms of acute narrow-angle glaucoma, including eye pain or
discomfort, blurred vision, visual halos or colored images in
association with red eyes from conjunctival congestion and corneal
edema.
Worsening of urinary retention may occur. Use with caution in
patients with prostatic hyperplasia or bladder-neck obstruction and
instruct patients to contact a healthcare provider immediately if
symptoms occur.
Immediate hypersensitivity reactions may occur after
administration of YUPELRI. If a reaction occurs, YUPELRI should be
stopped at once and alternative treatments considered.
The most common adverse reactions occurring in clinical trials
at an incidence greater than or equal to 2% in the YUPELRI group,
and higher than placebo, included cough, nasopharyngitis, upper
respiratory infection, headache and back pain.
Coadministration of anticholinergic medicines or OATP1B1 and
OATP1B3 inhibitors with YUPELRI is not recommended.
YUPELRI is not recommended in patients with any degree of
hepatic impairment.
Please see the full Prescribing
Information.
For additional information please contact us
at 800-395-3376.
You are encouraged to report negative side effects of
prescription drugs to the FDA.
Visit www.fda.gov/medwatch or
call 1-800-FDA-1088.
About Theravance Biopharma
Theravance
Biopharma, Inc. ("Theravance Biopharma") is a diversified
biopharmaceutical company primarily focused on the discovery,
development and commercialization of organ-selective medicines. Our
purpose is to create transformational medicines to improve the
lives of patients suffering from serious illnesses. Our research is
focused in the areas of inflammation and immunology.
In pursuit of our purpose, we apply insights and innovation at
each stage of our business and utilize our internal capabilities
and those of partners around the world. We apply organ-selective
expertise to biologically compelling targets to discover and
develop medicines designed to treat underserved localized diseases
and to limit systemic exposure, in order to maximize patient
benefit and minimize risk. These efforts leverage years of
experience in developing lung-selective medicines to treat
respiratory disease, including FDA-approved YUPELRITM (revefenacin)
inhalation solution indicated for the maintenance treatment of
patients with chronic obstructive pulmonary disease (COPD). Our
pipeline of internally discovered programs is targeted to address
significant patient needs.
We have an economic interest in potential future payments from
Glaxo Group or one of its affiliates (GSK) pursuant to its
agreements with Innoviva, Inc. relating to certain programs,
including TRELEGY ELLIPTA.
For more information, please visit www.theravance.com.
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 (including the data therefrom), the potential
characteristics, benefits and mechanisms of action of the Company's
product and product candidates, and the Company's expectations for
product candidates through development and potential regulatory
approval and commercialization (including their potential as
components of combination therapies and their differentiation from
other products or potential products). 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, enrolling
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), risks
that product candidates do not obtain approval from regulatory
authorities, the feasibility of undertaking future clinical trials
for our product candidates based on policies and feedback from
regulatory authorities, 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, manufacture
and commercialize products, 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 10, 2019 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 more than 40% of people being treated for
HIV/AIDS globally 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
approximately 35,000-strong workforce is dedicated to creating
better health for a better world, one person at a time. Learn more
at Mylan.com. We routinely post information that may be
important to investors on our website
at investor.mylan.com.
This press release includes statements that constitute
"forward-looking statements," including with regard to the outcome
of clinical trials. These statements are made pursuant to the safe
harbor provisions of the Private Securities Litigation Reform Act
of 1995. Because forward-looking statements inherently involve
risks and uncertainties, actual future results may differ
materially from those expressed or implied by such
statements. Factors that could cause or contribute to such
differences include, but are not limited to any changes in,
interruptions to, or difficulties with Mylan's or its partners'
ability to develop, manufacture, and commercialize products; the
effect of any changes in Mylan's or its partners' customer and
supplier relationships and customer purchasing patterns; other
changes in third-party relationships; the impact of competition;
changes in the economic and financial conditions of the businesses
of Mylan or its partners; the scope, timing, and outcome of any
ongoing legal proceedings and the impact of any such proceedings on
Mylan's or its partners' business; any regulatory, legal, or other
impediments to Mylan's or its partners' ability to bring products
to market; actions and decisions of healthcare and pharmaceutical
regulators, and changes in healthcare and pharmaceutical laws and
regulations, in the United States
and abroad; Mylan's and its partners' ability to protect
intellectual property and preserve intellectual property rights;
risks associated with international operations; other 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).
2 American Lung Association. "Chronic Obstructive
Pulmonary Disease
(COPD)" http://www.lung.org/lung-health-and-diseases/lung-disease-lookup/copd.
Accessed on May 13, 2019.
3 Center for Disease Control,
COPD https://www.cdc.gov/copd/index.html. Accessed on
May 13, 2019.
4 TBPH market research (N = 160 physicians); Refers
to US COPD patients.
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SOURCE Mylan N.V.; Theravance Biopharma, Inc.