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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 34 th 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 ):
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:
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 US 4 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).
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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).
SOURCE Theravance Biopharma, Inc.