DUBLIN, Nov. 16,
2023 /PRNewswire/ -- Theravance Biopharma,
Inc. ("Theravance Biopharma" or the "Company") (NASDAQ: TBPH)
today announced that a new, anchor-based analysis of ampreloxetine
data in neurogenic orthostatic hypotension (nOH) will be presented
at the 34th International Symposium on The Autonomic
Nervous System, a meeting of the American Autonomic Society (AAS),
taking place November 15-18, 2023, in
Rio Grande, Puerto Rico. Anchor-based analyses help establish
thresholds used to interpret the clinical meaningfulness of changes
in patient-reported outcomes measures such as the Orthostatic
Hypotension Questionnaire (OHQ).
"The results of this anchor-based analysis of prior
ampreloxetine studies underscore the clinical relevance of the
Orthostatic Hypotension Symptom Assessment domain of the
Orthostatic Hypotension Questionnaire and further substantiate its
use as a primary endpoint in clinical studies," said Horacio Kaufmann, M.D., Felicia B. Axelrod
Professor of Dysautonomia Research, Department of Neurology
at New York University School of
Medicine. "Those suffering from symptoms of nOH could benefit
greatly from the availability of new therapies and identifying
clinically meaningful changes in outcome measures is critical to
bringing new medicines forward for nOH."1
Data will be presented in a poster session on Thursday, November 16, 2023, starting at
7:00 PM Atlantic Standard Time
(3:00 PM PST / 6:00 PM EST / 11:00 PM
GMT):
- Kaufmann H, et al.
Poster #95
Evaluating clinically meaningful changes in the Orthostatic
Hypotension Symptom Assessment domain of the Orthostatic
Hypotension Questionnaire
Data Presented at the 2023 AAS Annual Meeting:
Key observations from this anchor-based analysis of the
ampreloxetine Phase 3 studies, Study 0169 [SEQUOIA] and Study 0170
[REDWOOD], include the following:
- Two measures of patient clinical status served as anchors to
the Orthostatic Hypotension Symptom Assessment (OHSA)
composite score for the analysis. Patient global assessment of
change (PGI-C) at Week 4 served as an anchor in Study 0169 and
patient global assessment of severity (PGI-S) at Week 6 of the
randomized withdrawal period served as an anchor in Study
0170.
- The OHSA composite score was shown to correlate with both
PGI-C and PGI-S, providing additional support for its use as an
appropriate endpoint when evaluating nOH symptoms.
- Clinically meaningful thresholds of an improvement of 0.9 to
1.3 points and a worsening of 0.7 to 1.1 points in the OHSA
composite score were identified.
Study Implications:
The 1.6 point benefit demonstrated by ampreloxetine relative to
placebo in multiple system atrophy (MSA) patients during the
randomized withdrawal period of Study 170 exceeds the OHSA
composite score thresholds established in the presented
analysis.2
The OHSA composite score was chosen as the primary efficacy
endpoint in the Phase 3 CYPRESS study, which is currently enrolling
patients. This anchor-based analysis model will aid in the
interpretation of clinically meaningful changes to the OHSA
composite score observed in CYPRESS. Further, establishment of an
anchor-based, clinically meaningful change in the OHSA composite
primary endpoint will be important for clinicians, regulators, and
payors.
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 dose of placebo or 10 mg 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).3 There are approximately 50,000 MSA
patients in the US4 and 70-90% of MSA patients
experience nOH symptoms.5 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),
the relevance of the anchor-based analysis model described above in
the interpretation of clinically meaningful changes to the OHSA
composite score observed in CYPRESS and the importance of the
establishment of an anchor-based, clinically meaningful change in
the OHSA composite primary endpoint to clinicians, regulators, and
payors. 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: 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 unexpected or 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, ,
ability to retain key personnel, 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 November 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.
Contact:
investor.relations@theravance.com
650-808-4045
1 Disclosure: Dr. Kaufmann is a paid consultant of
Theravance Biopharma US, Inc. and received consulting fees from
Theravance Biopharma US, Inc. related to this presentation.
2 Data from MSA patients at week 6 of the randomized
withdrawal period of Study 0170.
3
https://medlineplus.gov/genetics/condition/multiple-system-atrophy/
4 UCSD Neurological Institute (25K-75K, with ~10K
new cases per year); NIH National Institute of Neurological
Disorders and Stroke (15K-50K).
5 Delveinsight MSA Market Forecast (2023); Symptoms
associated with orthostatic hypotension in pure autonomic failure
and multiple systems atrophy, CJ Mathias (1999).
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