Full Press Release Details
Theravance Biopharma, Inc. Announces
Results from Study 0170, a Second Phase 3 Study of Ampreloxetine, in Patients with Symptomatic Neurogenic Orthostatic Hypotension (nOH)
DUBLIN, April 4, 2022 /PRNewswire/
-- Theravance Biopharma, Inc. ("Theravance Biopharma" or the "Company") (NASDAQ: TBPH) today announced
results from the second Phase 3 study, Study 0170 (n=128 out of n=154 planned), assessing the durability of clinical effect of ampreloxetine
compared to placebo for the treatment of symptomatic nOH. Study 0170 was a 22-week Phase 3 study comprised of a 16-week open-label
period followed by a 6-week double-blind, placebo-controlled, randomized withdrawal period. The primary endpoint of treatment failure
at week 6 of the randomized withdrawal period was defined as a worsening of both Orthostatic Hypotension Symptom Assessment Scale (OHSA)
question #1 and Patient Global Impression of Severity (PGI-S) scores by 1.0 point.
The primary endpoint was not
statistically significant for the overall population of patients which included patients with Parkinson's disease (PD),
pure autonomic failure (PAF) and MSA (odds ratio=0.6; p-value=0.196). The odds ratio suggests that
patients receiving ampreloxetine had a 40% reduction in the odds of treatment failure compared
The pre-specified subgroup analysis by disease type suggests the benefit
seen in patients receiving ampreloxetine was largely driven by MSA patients (n=40). An odds ratio of 0.28 (95% CI: 0.05, 1.22) was observed
in MSA patients indicating a 72% reduction in the odds of treatment failure with ampreloxetine compared to placebo. The benefit to MSA
patients was observed in multiple endpoints including OHSA composite, Orthostatic Hypotension Daily Activities Scale (OHDAS) composite,
Orthostatic Hypotension Questionnaire (OHQ) composite and OHSA #1 (see figure below). Notably, patients withdrawn to placebo had a clinically
relevant decrease in standing blood pressure; there was no decrease for patients remaining on ampreloxetine.
While the same benefit was not apparent in patients with PD or PAF, the Company continues to analyze the data to better understand this
observation. Throughout the study, there was no indication of worsening of supine hypertension based on 24-hour monitoring. Data suggest
that ampreloxetine was well-tolerated and no new safety signals were identified.
OHQ questionnaire Composite scores and individual items for MSA
"MSA is a devastating
and debilitating disease with no effective disease modifying treatment. There is an urgency to treat MSA patients suffering with nOH
due to the impact on quality of life and the extreme caregiver burden. Ampreloxetine appears to improve a narrow, but critically important
group of symptoms related to blood pressure control, and along with the safety profile, may represent a potential therapy for MSA patients,"
said Roy Freeman, MBChB, Professor of Neurology, Director, Center for Autonomic and Peripheral Nerve Disorders, Beth Israel Deaconess
Medical Center, who assisted in the design and interpretation of the study.
"At Theravance Biopharma,
we are guided by patient outcomes. Given the clear unmet need for MSA patients suffering from symptomatic nOH, we are engaging potential
partners and planning health authority interactions to determine a path forward in hopes of expediting ampreloxetine as a possible treatment
option for people with MSA," said Rick E Winningham, Chief Executive Officer, Theravance Biopharma. "Concurrently,
we are executing against our business plan and remain disciplined in capital allocation, maximizing shareholder value and re-iterate
our goal to be sustainably cash-flow positive by the second half of this year."
Dr. Freeman is a consultant serving as an advisor for drug development and clinical trial design for Theravance Biopharma.
Study 0170 (REDWOOD) Ampreloxetine
About the Phase 3 Study
Study 0170 (NCT03829657) was a 22-week Phase 3 study comprised of a 16-week open-label period
and a 6-week double-blind, placebo-controlled, randomized withdrawal period. The primary endpoint of treatment failure at week 6 was
defined as a worsening of both Orthostatic Hypotension Symptom Assessment Scale (OHSA) question #1 and Patient Global Impression of Severity
(PGI-S) scores by 1.0 point. After Study 0169 did not meet its primary endpoint, the Company took actions to close out the ongoing clinical
program including Study 0170. The study was more than 80% enrolled (n=128/154 planned) despite
About Symptomatic nOH
Neurogenic orthostatic hypotension (nOH) is a rare disorder defined as a sustained orthostatic fall in systolic blood pressure (SBP)
of 20 mm Hg or diastolic blood pressure (DBP) of 10 mm Hg within three minutes of standing. Severely affected patients are
unable to stand for more than a few seconds because of their decrease in blood pressure, leading to cerebral hypoperfusion and syncope.
A debilitating condition, nOH results in a range of symptoms including dizziness, lightheadedness, fainting, fatigue, blurry vision,
weakness, trouble concentrating, and head and neck pain. nOH is caused by autonomic nervous system malfunction and is associated with
several underlying medical conditions including multiple system atrophy (MSA), pure autonomic failure (PAF), and Parkinson's disease
About Multiple System Atrophy
MSA (formerly Shy-Drager syndrome) is a rare, rapidly
progressive, severely debilitating, and fatal neurodegenerative disease that leads to death within a median of seven to 10 years after
the onset of symptoms. MSA shares many Parkinson's disease-like symptoms, such as slow movement, rigid muscles and poor balance.
The primary sign of multiple system atrophy is postural (orthostatic) hypotension. A person with MSA can also develop dangerously high
blood pressure levels while lying down (supine hypertension). Other manifestations include: urinary and bowel dysfunction, constipation,
incontinence, sweating abnormalities, sleep disorders, sexual dysfunction, cardiovascular problems and psychiatric problems. The most
common causes of death in MSA are infection and cardiopulmonary complications. Currently, MSA patients receive only symptomatic and palliative
therapies as there are no disease-modifying treatments and no cure.
Ampreloxetine (TD-9855) is an investigational, Theravance Biopharma-discovered, potent, long-acting, oral, once-daily norepinephrine
reuptake inhibitor in development for the treatment of symptomatic neurogenic orthostatic hypotension (nOH) with patent protection until
2037 in the US. In addition to the Phase 3 clinical program, Theravance Biopharma has conducted a comprehensive non-clinical and clinical
pharmacology program. Ampreloxetine has been evaluated in over 800 patients in clinical studies of fibromyalgia, attention deficit hyperactivity
disorder (ADHD) and symptomatic nOH.
Theravance Biopharma
Theravance Biopharma, Inc. is a biopharmaceutical company primarily focused on the discovery, development and commercialization
of respiratory medicines. Its core purpose is to create medicines that help improve the lives of patients suffering from respiratory
pursuit of its purpose, Theravance Biopharma leverages decades of respiratory expertise to discover and develop transformational
medicines that make a difference. These efforts have led to the development of FDA-approved YUPELRI (revefenacin)
inhalation solution indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD). Its respiratory
pipeline of internally discovered programs is targeted to address significant patient respiratory needs.
Biopharma has an economic interest in potential future payments from Glaxo Group Limited or one of its affiliates (GSK)
pursuant to its agreements with Innoviva, Inc. relating to certain programs, including TRELEGY.
more information, please visit www.theravance.com.
BIOPHARMA , THERAVANCE , and the Cross/Star logo are registered trademarks of the Theravance Biopharma group
of companies (in the US and certain other countries).
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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, 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 goals, designs, strategies, plans and objectives, ability to provide value
to shareholders, the Company's regulatory strategies, the potential characteristics, benefits and mechanisms of action of the Company's
product and product candidates, the Company's expectations for product candidates through development and the market for products
being commercialized, the Company's expectations regarding its allocation of resources, potential regulatory actions and commercialization,
product sales or profit share revenue and the Company's expectations for its expenses, excluding share-based compensation and other
financial results. 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: additional future analysis of the data resulting from our clinical trial(s), the potential that
results from clinical or non-clinical studies indicate the Company's compounds, products or product candidates are unsafe, ineffective
or not differentiated, risks of decisions from regulatory authorities that are unfavorable to the Company, 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 ability to retain key personnel, the impact of the Company's restructuring actions
on its employees, partners and others. In addition, while we expect the effects of COVID-19 to continue to adversely impact our business
operations and financial results, the extent of the impact on our ability to generate revenue from YUPELRI (revefenacin),
our clinical development programs, and the value of and market for our ordinary shares, will depend on future developments that are highly