Theravance Biopharma Completes Enrollment in Pivotal Phase 3 CYPRESS Study of Ampreloxetine in Patients with Symptomatic Neurogenic Orthostatic Hypotension due to Multiple System Atrophy
Theravance Biopharma (NASDAQ: TBPH) has completed enrollment in its pivotal Phase 3 CYPRESS study of ampreloxetine for treating symptomatic neurogenic orthostatic hypotension (nOH) in patients with multiple system atrophy (MSA). The study targets an underserved population of approximately 40,000 U.S. patients.
The CYPRESS trial is a global, randomized-withdrawal study with a 12-week open-label portion followed by an 8-week randomized phase. The company expects topline results in Q1 2026 and plans to pursue an expedited NDA submission with potential priority FDA review. Ampreloxetine has received Orphan Drug Designation in the U.S., highlighting the significant unmet need in treating nOH due to MSA.
Theravance Biopharma (NASDAQ: TBPH) ha completato il reclutamento nello studio pivotale di Fase 3 CYPRESS su ampreloxetina per il trattamento dell'ipotensione ortostatica neurogena sintomatica (nOH) in pazienti con atrofia multisistemica (MSA). Lo studio riguarda una popolazione poco servita di circa 40.000 pazienti negli Stati Uniti.
Il trial CYPRESS è uno studio globale a ritiro randomizzato con una fase in aperto di 12 settimane seguita da una fase randomizzata di 8 settimane. L'azienda prevede risultati principali nel primo trimestre 2026 e intende perseguire una sottomissione NDA accelerata con possibile revisione prioritaria da parte della FDA. Ampreloxetina ha ricevuto la Designazione di Farmaco Orfano negli Stati Uniti, a sottolineare l'importante bisogno terapeutico insoddisfatto nella nOH dovuta a MSA.
Theravance Biopharma (NASDAQ: TBPH) ha completado la inscripción en su estudio pivotal de Fase 3 CYPRESS con ampreloxetina para el tratamiento de la hipotensión ortostática neurogénica sintomática (nOH) en pacientes con atrofia de sistemas múltiples (MSA). El estudio se dirige a una población desatendida de aproximadamente 40,000 pacientes en EE. UU.
El ensayo CYPRESS es un estudio global de retirada aleatorizada con una fase abierta de 12 semanas seguida de una fase aleatorizada de 8 semanas. La compañía espera resultados principales en el primer trimestre de 2026 y planea solicitar una presentación acelerada de NDA con posible revisión prioritaria por la FDA. Ampreloxetina ha recibido la Designación de Fármaco Huérfano en EE. UU., lo que destaca la importante necesidad no cubierta en el tratamiento de la nOH por MSA.
Theravance Biopharma (NASDAQ: TBPH)는 다계통 위축증(MSA) 환자의 증상성 신경인성 기립성 저혈압(nOH) 치료를 위한 암프렐록세틴의 중추 임상 3상 CYPRESS 연구에서 등록을 완료했습니다. 이 연구는 미국에서 약 40,000명에 달하는 의료 혜택을 덜 받는 인구를 대상으로 합니다.
CYPRESS 시험은 12주간의 개방형(오픈라벨) 기간 후 8주간의 무작위 철회(랜덤화) 단계로 구성된 글로벌 연구입니다. 회사는 2026년 1분기 주요 결과를 예상하고 있으며, FDA의 우선 심사를 받을 수 있는 신속 NDA 제출을 추진할 계획입니다. 암프렐록세틴은 미국에서 희귀의약품 지정(Orphan Drug Designation)을 받아 MSA로 인한 nOH 치료에 대한 중대한 미충족 수요를 강조합니다.
Theravance Biopharma (NASDAQ: TBPH) a terminé le recrutement dans son étude pivot de Phase 3 CYPRESS évaluant l'ampreloxétine pour le traitement de l'hypotension orthostatique neurogène symptomatique (nOH) chez des patients atteints d'atrophie multisystémique (MSA). L'étude cible une population peu prise en charge d'environ 40 000 patients aux États-Unis.
Le essai CYPRESS est une étude mondiale de type randomised-withdrawal comportant une période ouverte de 12 semaines suivie d'une phase randomisée de 8 semaines. La société prévoit des résultats principaux au 1er trimestre 2026 et envisage une soumission NDA accélérée avec un éventuel examen prioritaire par la FDA. L'ampreloxétine a obtenu la Désignation de Médicament Orphelin aux États-Unis, soulignant le besoin thérapeutique important non satisfait pour la nOH liée à la MSA.
Theravance Biopharma (NASDAQ: TBPH) hat die Einschreibung in seine entscheidende Phase-3-Studie CYPRESS mit Ampreloxetin zur Behandlung der symptomatischen neurogenen orthostatischen Hypotonie (nOH) bei Patienten mit multipler Systematrophie (MSA) abgeschlossen. Die Studie richtet sich an eine unterversorgte Patientengruppe von etwa 40.000 Personen in den USA.
Die CYPRESS-Studie ist eine weltweit durchgeführte Randomized-Withdrawal-Studie mit einem 12-wöchigen offenen Abschnitt, gefolgt von einer 8-wöchigen randomisierten Phase. Das Unternehmen erwartet Topline-Ergebnisse im 1. Quartal 2026 und plant eine beschleunigte NDA-Einreichung mit möglicher priorisierter Prüfung durch die FDA. Ampreloxetin hat in den USA die Orphan-Drug-Zulassung erhalten, was den erheblichen ungedeckten Bedarf bei der Behandlung von nOH durch MSA unterstreicht.
- Completed enrollment in Phase 3 CYPRESS study ahead of Q1 2026 topline results
- Ampreloxetine has Orphan Drug Designation status in the U.S.
- Previous Study 0170 showed compelling improvement in OHSA composite score without worsening supine hypertension
- Targeting large addressable market of 40,000 U.S. patients with MSA-associated nOH
- Results not expected until Q1 2026
- Open-label study design may introduce bias
- Success dependent on positive Phase 3 results and subsequent FDA approval
Insights
Theravance's completion of Phase 3 enrollment for ampreloxetine represents significant progress toward addressing an unmet need in MSA patients with nOH.
Theravance Biopharma has reached a significant clinical milestone with the completed enrollment in their pivotal Phase 3 CYPRESS study of ampreloxetine for neurogenic orthostatic hypotension (nOH) in multiple system atrophy (MSA) patients. This development is particularly noteworthy as it targets a specific orphan indication affecting approximately
The study design shows careful strategic planning based on previous data. This randomized-withdrawal methodology - where responders from the open-label portion are randomized to continue treatment or switch to placebo - is particularly well-suited for demonstrating durable efficacy in chronic conditions. This approach leverages insights from their previous Study 0170, which showed promising improvements in OHSA composite scores without worsening supine hypertension.
What sets ampreloxetine apart is its mechanism of action targeting the underlying pathophysiology of nOH through selective norepinephrine reuptake inhibition. Current treatments for nOH often have limitations including frequent dosing requirements and safety concerns such as supine hypertension. If successful, ampreloxetine could offer advantages in both efficacy and safety profile.
The company's timeline indicates topline results in Q1 2026 with plans for expedited NDA submission. The Orphan Drug Designation provides regulatory advantages and market protection if approved. With the planned request for priority FDA review, Theravance is positioning this asset for an accelerated path to market - a potential value driver given the lack of effective treatments specifically designed for nOH in MSA patients.
The completion of enrollment in Theravance's CYPRESS trial addresses a critical therapeutic gap in MSA-associated nOH management. MSA is a particularly aggressive neurodegenerative disorder with limited treatment options, and nOH affects approximately
Current nOH treatments are suboptimal for several reasons. They typically provide only transient symptom relief, require multiple daily doses affecting compliance, and often cause dangerous supine hypertension (leading to boxed warnings). The statement from Dr. Kaufmann, a leading authority in autonomic disorders, highlighting ampreloxetine's potential to become first-line therapy for most MSA patients with nOH, carries substantial weight in the neurological community.
The mechanistic approach of ampreloxetine is particularly promising. By selectively inhibiting norepinephrine reuptake, it addresses the core pathophysiology of nOH in MSA - namely, the failure of peripheral noradrenergic neurons to release sufficient norepinephrine to maintain adequate vasoconstriction upon standing. The preliminary data from Study 0170 showing improvements in the OHSA composite score without worsening supine hypertension suggests a potentially differentiated safety profile.
The randomized-withdrawal study design is scientifically robust and appropriate for this indication. By first establishing response in an open-label phase and then demonstrating maintenance of effect versus placebo withdrawal, CYPRESS should provide compelling evidence of durable efficacy if successful. This would represent a significant advancement for a patient population with severely limited options and high unmet need.
- Topline results anticipated in Q1 2026 and, if successful, planning for expedited NDA submission
- If approved, ampreloxetine could address a critical unmet need as the first therapy with the potential to provide durable benefit for the 40,000 patients in the
U.S. with symptomatic neurogenic orthostatic hypotension (nOH) in patients with multiple system atrophy (MSA) - Ampreloxetine has Orphan Drug Designation in the
U.S. , underscoring the unmet need in symptomatic nOH due to MSA
"nOH is one of the most debilitating manifestations of MSA, which affects about 40,000 patients in the
The registration-enabling Phase 3 CYPRESS (NCT05696717) study is a global, randomized-withdrawal study evaluating ampreloxetine in patients with symptomatic nOH due to clinically diagnosed MSA. Patients were enrolled in the 12-week open-label portion of the study at sites across four continents. At the end of the open-label portion, responders are randomized 1:1 to continue ampreloxetine or switch to placebo for eight weeks in the randomized-withdrawal portion of the study. The primary endpoint is change in orthostatic hypotension symptom assessment (OHSA) composite score from randomized-withdrawal baseline to Week 8.
"Completing enrollment in CYPRESS marks a major step toward bringing this potentially transformative therapy to patients with symptomatic nOH due to MSA – an underserved patient population in dire need for a new, effective and durable treatment with a favorable safety profile," said Áine Miller, Ph.D., Head of Development at Theravance Biopharma. "Ampreloxetine is intended to target the root cause driving MSA-associated nOH by selectively inhibiting norepinephrine reuptake, and demonstrated benefit in this patient population in Study 0170. The CYPRESS randomized withdrawal trial was designed with insights from Study 0170, and we are confident that, along with our careful study execution, this derisked program strongly positions us to evaluate ampreloxetine's full potential in this patient population."
The Company expects to report topline data from the Phase 3 CYPRESS trial in Q1 2026. In parallel, Theravance is preparing for an expedited NDA submission following the results and is planning to request priority FDA review, if data are supportive. This milestone reinforces our strategic focus and delivers on Theravance's commitment to advancing high-impact catalysts, as previously highlighted in our recent Q2 earnings call.
About Ampreloxetine
Ampreloxetine, an investigational, once-daily, selective 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 worsening of supine hypertension. In the US, the Company has been granted an Orphan Drug Designation for ampreloxetine for the treatment of symptomatic nOH in patients with MSA and, if results from the ongoing Phase 3 CYPRESS study are supportive, plans to file an NDA for full approval in this indication.
About the Phase 3 CYPRESS (Study 0197) Study
The CYPRESS Study (NCT05696717) 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 the Phase 3 SEQUOIA (Study 0169) and REDWOOD (Study 0170) Studies
Study 0169 (NCT03750552) was a Phase 3, 4-week, multi-center, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of ampreloxetine compared to placebo in patients with symptomatic nOH (n=195). Patients from Study 0169 were eligible to enter into Study 0170 (NCT03829657), a Phase 3, multi-center, 22-week study comprising a 16-week open-label period and a 6-week double-blind, placebo-controlled, randomized withdrawal period to evaluate the sustained benefit in efficacy and safety 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
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
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 once-daily norepinephrine reuptake inhibitor in development for symptomatic neurogenic orthostatic hypotension (nOH) in patients with Multiple System Atrophy (MSA), has the potential to be a first in class therapy effective in treating a constellation of cardinal symptoms in MSA 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.
Dr. Kaufmann is a member of an advisory committee supporting the CYPRESS clinical trial and a paid consultant to Theravance Biopharma.
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, Inc. (the "Company") 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 expectations regarding its future profitability, expenses and uses of cash, the Company's goals, designs, strategies, plans and objectives, future growth of YUPELRI sales, future royalty payments, the ability to provide value to shareholders, the Company's regulatory strategies and timing of clinical studies, possible safety, efficacy or differentiation of our investigational therapy, the status of patent infringement litigation initiated by the Company and its partner against certain generic companies in federal district courts; contingent payments due to the Company from the sale of the Company's TRELEGY ELLIPTA royalty interests to Royalty Pharma, and expectations around the use of OHSA scores as endpoints for clinical trials. 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 the conference call 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: factors that could increase the Company's cash requirements or expenses beyond its expectations and any factors that could adversely affect its profitability, 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, 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 13, 2025, 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 https://www.medrxiv.org/content/10.1101/2025.08.12.25332833v1 Precision therapy with ampreloxetine for neurogenic orthostatic hypotension in multiple system atrophy
Roy Freeman, Horacio Kaufmann, Italo Biaggioni, Valeria Iodice, Jens Jordan, Ross Vickery, Tadhg Geurin, Matthew J. Kmiecik, Lucy Norcliffe-Kaufmann
2https://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).
View original content to download multimedia:https://www.prnewswire.com/news-releases/theravance-biopharma-completes-enrollment-in-pivotal-phase-3-cypress-study-of-ampreloxetine-in-patients-with-symptomatic-neurogenic-orthostatic-hypotension-due-to-multiple-system-atrophy-302537380.html
SOURCE Theravance Biopharma, Inc.
FAQ
What is the expected timeline for Theravance's (TBPH) Phase 3 CYPRESS trial results?
How many patients could benefit from Theravance's ampreloxetine treatment?
What is the design of TBPH's Phase 3 CYPRESS trial for ampreloxetine?
What regulatory designations has Theravance's ampreloxetine received?
What were the results from Theravance's previous Study 0170 for ampreloxetine?
