DUBLIN, Aug. 28,
2023 /PRNewswire/ -- Theravance Biopharma,
Inc. ("Theravance Biopharma" or the "Company") (NASDAQ: TBPH)
today announced new ampreloxetine data in neurogenic orthostatic
hypotension (nOH) will be presented at the 2023 International
Congress of Parkinson's Disease and Movement Disorders (MDS),
taking place August 27-31, 2023, in
Copenhagen, Denmark.
"The data presented at this meeting continue to support
ampreloxetine's potential to deliver a consistent and durable
benefit to MSA patients with nOH with a favorable safety and
tolerability profile," said Roy
Freeman, MBChB, Professor of Neurology, Director, Center for
Autonomic and Peripheral Nerve Disorders, Beth Israel Deaconess
Medical Center. "MSA is a rare, debilitating disease and
many MSA patients suffer from symptoms related to poor blood
pressure control that have a significant impact on their quality of
life."1
Data will be presented in a poster session on Monday, August 28, 2023, starting at 1:00 PM Central European Time (7:00 AM EDT / 4:00 AM
PDT / 11:00 AM GMT):
Category: Clinical Trials and Therapy in Movement Disorders
(non-PD) (non-Dystonia)
- Freeman R, et al. Abstract
7
An Analysis of Subgroups of Multiple System Atrophy Patients
from Ampreloxetine Phase 3 Trials
- Borin M, et al.
Abstract 3
A Multiple-dose Thorough QT Study to Evaluate the Effect
of Ampreloxetine on Cardiac Repolarization in Healthy
Subjects
Findings Presented at the 2023 MDS Congress:
Ampreloxetine demonstrated the following benefits in MSA
(multiple system atrophy) patients from studies 0169 [SEQUOIA] and
0170 [REDWOOD]:
- Clinically-meaningful and nominally statistically significant
(p< 0.05) improvements over placebo were observed in the
Orthostatic Hypotension Symptom Assessment (OHSA) composite score
[LS mean difference: -1.6 (95% CI: -2.7, -0.5)] and in the overall
Orthostatic Hypotension Questionnaire (OHQ) composite score [LS
mean difference: -1.2 (95%CI: -2.3, -0.2)] in Study 0170.
- Post-hoc analysis of Study 0170 indicated a consistent benefit
of ampreloxetine relative to placebo across MSA subgroups including
MSA sub-type (MSA-P and MSA-C), sex, age, time since MSA diagnosis,
time since nOH onset, and the global MSA disability scale (UMSARS
Part IV). Subgroup benefits of ampreloxetine ranged from 0.5 to 2.2
point improvements relative to placebo across all subgroup
categories and were demonstrated on the OHSA and OHQ composite
scores.
- Ampreloxetine was well-tolerated with similar adverse event
rates compared to placebo during the placebo-controlled periods of
both Study 0169 and Study 0170.
In a separate single-center study
evaluating ampreloxetine's effects on cardiac repolarization
compared to placebo, 72 healthy subjects were enrolled in a
randomized, double-blind, placebo-controlled fashion. At
therapeutic (10 mg QD) and supratherapeutic (40 mg QD) doses of
ampreloxetine, no clinically relevant effect on the Q-Tc interval,
a measure of heart rhythm, was observed in this study, further
supporting the cardiovascular safety of ampreloxetine.
About Ampreloxetine
Ampreloxetine, an investigational, once-daily norepinephrine
reuptake inhibitor in development for the treatment of symptomatic
neurogenic orthostatic hypotension (nOH) in patients with multiple
system atrophy (MSA). The unique benefits of ampreloxetine
treatment reported in MSA patients from Study 0170 included an
increase in norepinephrine levels, a favorable impact on blood
pressure, clinically meaningful and durable symptom improvement,
and no signal for supine hypertension. The company has been granted
an orphan drug designation in the US and, if results support it,
plans to file an NDA for full approval based on the Phase 3 CYPRESS
study.
About CYPRESS (Study 0197), a Phase 3 Study
Study 0197 (NCT05696717) is currently enrolling. This is a
registrational Phase 3, multi-center, randomized withdrawal study
to evaluate the efficacy and durability of ampreloxetine in
participants with MSA and symptomatic nOH after 20 weeks of
treatment; the primary endpoint of the study is change in the
Orthostatic Hypotension Symptom Assessment (OHSA) composite score.
The Study includes four periods: screening, open label (12-week
period, participants will receive a single daily 10 mg dose of
ampreloxetine), randomized withdrawal (eight-week period,
double-blind, placebo-controlled, participants will receive a
single daily 10 mg dose of placebo or ampreloxetine), and a
long-term treatment extension. Secondary outcome measures include
change from baseline in Orthostatic Hypotension Daily Activity
Scale (OHDAS) item 1 (activities that require standing for a short
time) and item 3 (activities that require walking for a short
time).
About Study 0170, a 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. This study
followed study 0169, a Phase 3, four week randomized, double-blind,
placebo-controlled, parallel-group study of ampreloxetine in
patients with symptomatic nOH. The primary endpoint for Study 0170
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 stopping early. The primary endpoint
was not statistically significant for the overall population of
patients which included patients with Parkinson's disease, pure
autonomic failure and MSA (odds ratio=0.6; p-value=0.196). 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 (read more about the data
here).
About Multiple System Atrophy (MSA) and Symptomatic
Neurogenic Orthostatic Hypotension (nOH)
MSA is a progressive brain disorder that affects movement and
balance and disrupts the function of the autonomic nervous system.
The autonomic nervous system controls body functions that are
mostly involuntary. One of the most frequent autonomic symptoms
associated with MSA is a sudden drop in blood pressure upon
standing (nOH).2 There are approximately 50,000 MSA
patients in the US3 and 70-90% of MSA patients
experience nOH symptoms.4 Despite available therapies,
many MSA patients remain symptomatic with nOH.
Neurogenic orthostatic hypotension (nOH) is a rare disorder
defined as a fall in systolic blood pressure of ⩾20 mm Hg or
diastolic blood pressure of ⩾10 mm Hg, within 3 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.
About Theravance Biopharma
Theravance Biopharma, Inc.'s focus is to
deliver Medicines that Make a
Difference® in people's lives. In pursuit of
its purpose, Theravance Biopharma leverages decades of
expertise, which has led to the development of FDA-approved
YUPELRI® (revefenacin) inhalation solution
indicated for the maintenance treatment of patients with chronic
obstructive pulmonary disease (COPD). Ampreloxetine, its late-stage
investigational norepinephrine reuptake inhibitor in development
for symptomatic neurogenic orthostatic hypotension, has the
potential to be a first in class therapy effective in treating a
constellation of cardinal symptoms in multiple system atrophy
patients. The Company is committed to creating/driving shareholder
value.
For more information, please visit www.theravance.com.
THERAVANCE BIOPHARMA®, THERAVANCE®, and
the Cross/Star logo are registered trademarks of
the Theravance Biopharma group of companies (in
the U.S. and certain other countries).
YUPELRI® is a registered trademark of Mylan Specialty
L.P., a Viatris company. Trademarks, trade names or service marks
of other companies appearing on this press release are the property
of their respective owners.
Forward-Looking Statements
This press release will contain 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, as amended, 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, 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, the
Company's expectations for product candidates through development
and potential regulatory approval and commercialization (including
their differentiation from other products or potential products)
and the Company's expectations regarding its allocation of
resources and maintenance of expenditures. These statements are
based on the current estimates and assumptions of the management of
Theravance Biopharma 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 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: whether the milestone thresholds can be achieved,
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 or
product are unsafe, ineffective or not differentiated, risks of
decisions from regulatory authorities that are unfavorable to the
Company, 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, ability to
retain key personnel, the impact of the Company's recent
restructuring actions on its employees, partners and others, the
ability of the Company to protect and to enforce its intellectual
property rights, volatility and fluctuations in the trading price
and volume of the Company's shares, and general economic and market
conditions. Other risks affecting the Company are in the Company's
Form 10-Q filed with the SEC on August 9,
2023, and other periodic reports filed 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.
1 Disclosure: Dr. Freeman is a consultant serving as
an advisor for drug development and clinical trial design for
Theravance Biopharma.
2
https://medlineplus.gov/genetics/condition/multiple-system-atrophy/
3 UCSD Neurological Institute (25K-75K, with ~10K
new cases per year); NIH National Institute of Neurological
Disorders and Stroke (15K-50K).
4 Delveinsight MSA Market Forecast (2023); Symptoms
associated with orthostatic hypotension in pure autonomic failure
and multiple systems atrophy, CJ Mathias (1999).
Contact:
investor.relations@theravance.com
650-808-4045
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