Theravance Biopharma Announces Ampreloxetine Presentations at the International MSA Congress
Theravance Biopharma (NASDAQ: TBPH) presented analyses of its Phase 3 program for ampreloxetine, a treatment for symptomatic neurogenic orthostatic hypotension (nOH), at the International MSA Congress. The subgroup analysis from the REDWOOD 0170 study showed that Multiple System Atrophy (MSA) patients experienced meaningful improvement in nOH symptoms after 16 weeks of treatment, with symptoms remaining stable in the ampreloxetine group while worsening in the placebo group.
Key findings revealed improved functional activities in treated patients and demonstrated ampreloxetine's sustained effect on standing blood pressure. Additional analysis from Study 0169 highlighted that MSA patients had the highest nOH symptom burden despite existing treatments, emphasizing the need for better therapies. These results support the ongoing CYPRESS registrational study in nOH and MSA patients.
Theravance Biopharma (NASDAQ: TBPH) ha presentato le analisi del suo programma di Fase 3 per ampreloxetine, un trattamento per l'ipotensione ortostatica neurogena sintomatica (nOH), al Congresso Internazionale sulla MSA. L'analisi del sottogruppo dello studio REDWOOD 0170 ha mostrato che i pazienti con Atrofia Multisistemica (MSA) hanno registrato un miglioramento significativo dei sintomi di nOH dopo 16 settimane di trattamento, con sintomi stabili nel gruppo trattato con ampreloxetine e peggioramento nel gruppo placebo.
I risultati principali hanno evidenziato un miglioramento delle attività funzionali nei pazienti trattati e hanno dimostrato l'effetto duraturo di ampreloxetine sulla pressione arteriosa in posizione eretta. Un'analisi aggiuntiva dello Studio 0169 ha sottolineato che i pazienti con MSA presentavano il carico sintomatico di nOH più elevato nonostante i trattamenti esistenti, evidenziando la necessità di terapie più efficaci. Questi risultati supportano lo studio di registrazione CYPRESS in corso su pazienti con nOH e MSA.
Theravance Biopharma (NASDAQ: TBPH) presentó análisis de su programa de Fase 3 para ampreloxetine, un tratamiento para la hipotensión ortostática neurogénica sintomática (nOH), en el Congreso Internacional de MSA. El análisis del subgrupo del estudio REDWOOD 0170 mostró que los pacientes con Atrofia de Múltiples Sistemas (MSA) experimentaron una mejora significativa en los síntomas de nOH tras 16 semanas de tratamiento, con síntomas estables en el grupo tratado con ampreloxetine y empeoramiento en el grupo placebo.
Los hallazgos clave revelaron una mejora en las actividades funcionales de los pacientes tratados y demostraron el efecto sostenido de ampreloxetine sobre la presión arterial en posición de pie. Un análisis adicional del Estudio 0169 destacó que los pacientes con MSA tenían la mayor carga de síntomas de nOH a pesar de los tratamientos existentes, subrayando la necesidad de mejores terapias. Estos resultados respaldan el estudio de registro CYPRESS en curso en pacientes con nOH y MSA.
Theravance Biopharma (NASDAQ: TBPH)는 증상성 신경인성 기립성 저혈압(nOH) 치료제인 ampreloxetine의 3상 프로그램 분석 결과를 국제 MSA 학회에서 발표했습니다. REDWOOD 0170 연구의 하위 그룹 분석 결과, 다계통 위축증(MSA) 환자들이 16주간 치료 후 nOH 증상이 유의미하게 개선되었으며, ampreloxetine 투여군에서는 증상이 안정적으로 유지된 반면 위약군에서는 악화된 것으로 나타났습니다.
주요 결과로는 치료받은 환자들의 기능적 활동 개선과 기립 혈압에 대한 ampreloxetine의 지속적인 효과가 확인되었습니다. 추가로 0169 연구 분석에서는 기존 치료에도 불구하고 MSA 환자들이 가장 높은 nOH 증상 부담을 가지고 있음을 강조하여 더 나은 치료법의 필요성을 부각시켰습니다. 이러한 결과는 nOH 및 MSA 환자를 대상으로 하는 진행 중인 CYPRESS 등록 연구를 뒷받침합니다.
Theravance Biopharma (NASDAQ : TBPH) a présenté des analyses de son programme de phase 3 pour ampreloxetine, un traitement de l'hypotension orthostatique neurogène symptomatique (nOH), lors du Congrès international sur la MSA. L'analyse de sous-groupe de l'étude REDWOOD 0170 a montré que les patients atteints d'atrophie multisystémique (MSA) ont connu une amélioration significative des symptômes de nOH après 16 semaines de traitement, avec des symptômes stables dans le groupe ampreloxetine tandis qu'ils s'aggravaient dans le groupe placebo.
Les résultats clés ont révélé une amélioration des activités fonctionnelles chez les patients traités et ont démontré l'effet durable de l'ampreloxetine sur la pression artérielle en position debout. Une analyse supplémentaire de l'étude 0169 a souligné que les patients atteints de MSA présentaient la charge symptomatique la plus élevée de nOH malgré les traitements existants, mettant en évidence le besoin de meilleures thérapies. Ces résultats soutiennent l'étude d'enregistrement CYPRESS en cours chez les patients atteints de nOH et de MSA.
Theravance Biopharma (NASDAQ: TBPH) stellte Analysen seines Phase-3-Programms für Ampreloxetin, eine Behandlung der symptomatischen neurogenen orthostatischen Hypotonie (nOH), auf dem Internationalen MSA-Kongress vor. Die Subgruppenanalyse der REDWOOD 0170-Studie zeigte, dass Patienten mit Multisystematrophie (MSA) nach 16 Wochen Behandlung eine deutliche Verbesserung der nOH-Symptome erfuhren, wobei die Symptome in der Ampreloxetin-Gruppe stabil blieben und in der Placebo-Gruppe sich verschlechterten.
Wesentliche Ergebnisse zeigten verbesserte funktionelle Aktivitäten bei behandelten Patienten und belegten die anhaltende Wirkung von Ampreloxetin auf den stehenden Blutdruck. Eine zusätzliche Analyse der Studie 0169 hob hervor, dass MSA-Patienten trotz bestehender Behandlungen die höchste Belastung durch nOH-Symptome hatten, was den Bedarf an besseren Therapien unterstreicht. Diese Ergebnisse unterstützen die laufende CYPRESS-Registrierungsstudie bei nOH- und MSA-Patienten.
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Insights
Phase 3 subgroup analysis shows ampreloxetine helps MSA patients with neurogenic orthostatic hypotension maintain symptom improvement compared to placebo.
Theravance Biopharma's Phase 3 REDWOOD trial subgroup analysis offers promising news for Multiple System Atrophy (MSA) patients who suffer from neurogenic orthostatic hypotension (nOH) - a condition causing dizziness and fainting upon standing due to blood pressure drops. The data showed clinically meaningful improvements in symptoms after 16 weeks of ampreloxetine treatment as measured by the OH Symptom Assessment composite score.
What's particularly encouraging is the durability of effect during the randomized withdrawal phase. Patients continuing ampreloxetine maintained their symptom improvements, while those switched to placebo deteriorated - providing strong evidence of the drug's sustained efficacy. They also maintained functional improvements in critical daily activities like standing or walking, which placebo patients lost.
The findings build a compelling clinical profile: ampreloxetine appears to effectively target residual peripheral autonomic neurons (the intended mechanism) and deliver sustained blood pressure stabilization when standing - exactly what we'd hope to see from a selective norepinephrine reuptake inhibitor in this condition.
Notably, a separate analysis revealed MSA patients experience the highest symptom burden among nOH sufferers even when taking currently available medications, highlighting the significant unmet need. These results provide strong rationale for the ongoing CYPRESS registrational trial specifically targeting MSA patients with nOH - a particularly difficult-to-treat population that could benefit substantially if ampreloxetine maintains this efficacy profile in the confirmatory study.
A subgroup analysis selected as a platform presentation focused on patients with Multiple System Atrophy (MSA) in the REDWOOD 0170 study (NCT03829657), an international phase 3, placebo-controlled, double-blind, randomized withdrawal trial, designed to demonstrate clinical worsening in those assigned to placebo. This analysis concluded:
- Patients with MSA showed clinically meaningful improvement in their nOH symptoms as measured by the OH Symptom Assessment (OHSA) composite score after 16 weeks of open-label treatment with ampreloxetine. After week 6 of randomization, symptoms remained stable in the ampreloxetine group and worsened in the placebo group.
- Ampreloxetine treatment was associated with an improvement in functional activities, such as standing or walking for a short time, which was lost after withdrawal to placebo.
- The clinical, cardiovascular and neuroendocrine profile of ampreloxetine showed target engagement of residual peripheral autonomic neurons and a sustained standing blood pressure effect, which is consistent with the profile of a selective norepinephrine reuptake inhibitor.
An additional analysis from Study 0169 (NCT03750552) presented at the Congress showed that despite treatment with available nOH medications, patients with MSA had the highest nOH symptom burden on entry, which highlights the substantial unmet need for better nOH therapies in this population.
Results from these studies were supportive of the current registrational study in patients with nOH and MSA that is currently ongoing (CYPRESS, NCT05696717).
"Patients with MSA often experience severe symptoms and impact to their quality of life due to nOH, and we are motivated to reduce this burden to patients and their caregivers," said Dr. Lucy Norcliffe-Kaufmann, Theravance Biopharma's Executive Director of Clinical Science. "As supported by a clinically-validated measure of patient well-being over 16 to 22 weeks of therapy, these analyses underpin our belief in ampreloxetine's potential to provide durable symptom relief with clinically meaningful outcomes."
Presentation information:
Ampreloxetine in MSA: A pre-specified subgroup analysis of a phase 3, double-blind, placebo-controlled, randomized withdrawal trial
- Norcliffe-Kaufmann L, et al. Oral Presentation May 9, 2025 - 9:40 AM EDT
- Norcliffe-Kaufmann L, et al. Poster #78 May 10, 2025 - 12:00 PM EDT
Impact of symptomatic neurogenic orthostatic hypotension on symptom burden and daily functioning in patients with alpha synucleinopathies
- Iodice V, et al. Poster #29 May 9, 2025 - 11:45 AM EDT
Slides presented by Dr. Norcliffe-Kaufmann may be found here in the Presentations section of Theravance Biopharma's website.
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 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 the ampreloxetine Phase 3 Program (Study 169 and Study 170)
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).[1] There are approximately 50,000 MSA patients in the US[2] and 70
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 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.
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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 Company's goals, designs, strategies, plans, potential, and objectives, the Company's regulatory strategies and timing of clinical studies, potential or possible safety, efficacy or differentiation of our investigational therapy, 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 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 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-K filed with the SEC on March 7, 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
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1 https://medlineplus.gov/genetics/condition/multiple-system-atrophy/
2 UCSD Neurological Institute (25K-75K, with ~10K new cases per year); NIH National Institute of Neurological Disorders and Stroke (15K-50K).
3 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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FAQ
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