ampreloxetine (TD-9855) / Theravance Biopharma, Royalty - LARVOL DELTA

The Impact of Ampreloxetine on Supine Hypertension: An Ambulatory Blood Pressure Monitoring Study. (S9.002). (PubMed, Neurology) - P3 | "The institution of Dr. Freeman has received research support from Lundbeck."

Clinical • Journal • Cardiovascular • CNS Disorders • Hypertension • Hypotension • Movement Disorders • Multiple System Atrophy • Parkinson's Disease

NET-Inhibition with Ampreloxetine, Blood Pressure, and Catecholamines in Patients with Neurogenic Orthostatic Hypotension (AAN 2025) - P3 | "The catecholamine profile observed on treatment with ampreloxetine showed target engagement of NE transporter-inhibition. After 16-weeks of open-label treatment, withdrawal of ampreloxetine was associated with a fall in standing BP. norepinephrine reuptake inhibition with ampreloxetine resulted in a sustained improvement in orthostatic BP, which was lost in patients that withdrew to placebo."

Clinical • Hypotension

The Impact of Ampreloxetine on Supine Hypertension: An Ambulatory Blood Pressure Monitoring Study. (AAN 2025) - P3 | "We saw no signal for worsening of supine hypertension on ampreloxetine in patients with alpha-synucleinopathies and nOH. This suggests that, if the ongoing phase 3 study confirms safety and efficacy, ampreloxetine may be the first drug to treat nOH without exacerbating supine hypertension, which should not worsen intravascular volume loss overnight or add to the risk of target organ damage."

Cardiovascular • CNS Disorders • Hypertension • Hypotension • Movement Disorders • Multiple System Atrophy • Parkinson's Disease

Long-term Safety of Ampreloxetine in Patients with Symptomatic Neurogenic Orthostatic Hypotension (MDS Congress 2024) - P3 | "The safety findings in this long-term study were consistent with the existing safety profile for ampreloxetine, with minimal incidences of related TEAEs and serious TEAEs. The low dropout rate and continuation of treatment for up to two years in this open-label extension study further supports the long-term safety and tolerability of ampreloxetine."

Clinical • CNS Disorders • Pain

Hepatic Dysfunction Quantified by HepQuant DuO Outperforms Child-Pugh Classification in Predicting the Pharmacokinetics of Ampreloxetine. (PubMed, Clin Pharmacol Ther) - "HepQuant DSI, SHUNT%, and hepatic reserve were more useful predictors of drug exposure than Child-Pugh class for ampreloxetine and thus may better optimize dose recommendations in patients with liver disease. The simple-to-administer, oral-only DuO version of the HepQuant test could enhance clinical utility."

Journal • PK/PD data • Hepatology • Liver Failure

Theravance Biopharma, Inc. to Host Virtual Key Opinion Leader (KOL) Event to Discuss Ampreloxetine's Potential for the Treatment of Symptomatic Neurogenic Orthostatic Hypotension (nOH) in Patients with Multiple System Atrophy (MSA) on May 23, 2024 (PRNewswire) - "Theravance Biopharma, Inc...announced it will host a virtual KOL event on Thursday, May 23, 2024 from 10:00 AM to 11:30 AM ET, featuring Horacio Kaufmann, MD, FAAN (Felicia B. Axelrod Professor of Neurology and Professor of Medicine at New York University Grossman School of Medicine) and Italo Biaggioni, MD (Professor of Medicine and Pharmacology Director, Vanderbilt Autonomic Dysfunction Center), who will discuss the unmet need and current treatment landscape for MSA patients with symptomatic nOH. The event will also feature presentations from the Company's CEO, Rick Winningham, Senior VP of Development, Aine Miller, and Chief Business Officer, Rhonda Farnum and will focus on the Company's clinical development program for ampreloxetine, an investigational, once-daily norepinephrine reuptake inhibitor with the potential to be a first-in-class therapy effective in treating a constellation of cardinal symptoms of nOH in MSA patients."

Clinical • CNS Disorders • Multiple System Atrophy • Rare Diseases

CYPRESS: Phase 3 Efficacy and Durability of Ampreloxetine for the Treatment of Symptomatic nOH in Participants With Multiple System Atrophy (clinicaltrials.gov) - P3 | N=102 | Recruiting | Sponsor: Theravance Biopharma

Trial completion date • Trial primary completion date • CNS Disorders • Hypotension • Movement Disorders • Multiple System Atrophy

Theravance Biopharma to Present New Ampreloxetine Data at the 2023 International Congress of Parkinson's Disease and Movement Disorders (PRNewswire) - P3 | N=203 | REDWOOD (NCT03829657) | Sponsor: Theravance Biopharma | "Theravance Biopharma, Inc...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....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."

P3 data • Retrospective data • CNS Disorders • Multiple System Atrophy • Rare Diseases

An Analysis of Subgroups of Multiple System Atrophy Patients from Ampreloxetine Phase 3 Trials (MDS Congress 2023) - "Ampreloxetine may be an effective treatment for symptomatic nOH in patients with MSA, with consistent benefits observed across key subgroups including MSA subtype, disease duration, sex and age."

Clinical • P3 data • CNS Disorders • Multiple System Atrophy

A multiple-dose thorough QT study to evaluate the effect of ampreloxetine on cardiac repolarization in healthy subjects (MDS Congress 2023) - "Ampreloxetine did not prolong the QTc interval at therapeutic or supratherapeutic dose levels to any clinically relevant extent."

Clinical • CNS Disorders • Epilepsy

CYPRESS: Phase 3 Efficacy and Durability of Ampreloxetine for the Treatment of Symptomatic nOH in Participants With Multiple System Atrophy (clinicaltrials.gov) - P3 | N=102 | Recruiting | Sponsor: Theravance Biopharma | Initiation date: Mar 2023 ➔ Jun 2023

Trial initiation date • CNS Disorders • Hypotension • Movement Disorders • Multiple System Atrophy

Ampreloxetine Versus Droxidopa in Neurogenic Orthostatic Hypotension: A Comparative Review. (PubMed, Cureus) - "Standing systolic BP was maintained by ampreloxetine and worsened after the withdrawal phase. This highlights the importance of conducting further research which will help us to improve the therapeutic approach for patients with nOH and Parkinson's disease."

Journal • Review • CNS Disorders • Hypotension • Movement Disorders • Parkinson's Disease

Theravance Biopharma, Inc. Announces Orphan Drug Designation Granted to Ampreloxetine for the Treatment of Symptomatic Neurogenic Orthostatic Hypotension in Patients with Multiple System Atrophy (PRNewswire) - "Theravance Biopharma, Inc...announced that the US Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) status to ampreloxetine for the treatment of symptomatic neurogenic orthostatic hypotension (nOH) in patients with multiple system atrophy (MSA). MSA is a rare neurodegenerative disorder in which patients suffer autonomic dysfunction affecting movement, balance, heart rate and blood pressure. Many patients with MSA suffer from the debilitating symptoms of nOH including dizziness, disrupted vision, muscle weakness, head and neck discomfort, and fatigue, which adversely affect quality of life."

Orphan drug • CNS Disorders • Multiple System Atrophy • Rare Diseases

CYPRESS: Phase 3 Efficacy and Durability of Ampreloxetine for the Treatment of Symptomatic nOH in Participants With Multiple System Atrophy (clinicaltrials.gov) - P3 | N=102 | Recruiting | Sponsor: Theravance Biopharma | Not yet recruiting ➔ Recruiting | Trial completion date: Jun 2027 ➔ Jan 2027 | Trial primary completion date: May 2025 ➔ Dec 2024

Enrollment open • Trial completion date • Trial primary completion date • CNS Disorders • Hypotension • Movement Disorders • Multiple System Atrophy

0197: Phase 3 Efficacy and Durability of Ampreloxetine for the Treatment of Symptomatic nOH in Participants With Multiple System Atrophy (clinicaltrials.gov) - P3 | N=102 | Not yet recruiting | Sponsor: Theravance Biopharma | Trial completion date: Dec 2025 ➔ Jun 2027 | Trial primary completion date: Oct 2025 ➔ May 2025

Trial completion date • Trial primary completion date • CNS Disorders • Hypotension • Movement Disorders • Multiple System Atrophy

0197: Phase 3 Efficacy and Durability of Ampreloxetine for the Treatment of Symptomatic nOH in Participants With Multiple System Atrophy (clinicaltrials.gov) - P3 | N=102 | Not yet recruiting | Sponsor: Theravance Biopharma

New P3 trial • CNS Disorders • Hypotension • Movement Disorders • Multiple System Atrophy

Theravance Biopharma, Inc. Highlights 2022 Accomplishments and 2023 Key Targets (PRNewswire) - "2023 Targets: Ampreloxetine: Initiate Phase 3 CYPRESS trial in MSA patients with symptomatic nOH in Q1 2023, targeting ~60 patients to complete the randomized withdrawal period. Submit orphan drug designation request in early 2023."

New P3 trial • Orphan drug • CNS Disorders • Multiple System Atrophy • Rare Diseases

Ampreloxetine Data in Neurogenic Orthostatic Hypotension to be Presented at the 33rd International Symposium on the Autonomic Nervous System (PRNewswire) - P3 | N=203 | REDWOOD (NCT03829657) | Sponsor: Theravance Biopharma | “Theravance Biopharma, Inc…today will present new ampreloxetine data in neurogenic orthostatic hypotension (nOH) from the Company's Phase 3 program at the 33rd International Symposium on the Autonomic Nervous System, a meeting of the American Autonomic Society (AAS)….Clinical Effectiveness of Ampreloxetine: Clinically meaningful and nominal statistically significant (p < 0.05) differences relative to placebo in MSA patients on the following endpoints in Study 0170: Orthostatic Hypotension Symptom Assessment Scale (OHSA) composite score (LS mean difference: -1.6 [95% CI: -2.7, -0.5]). Orthostatic Hypotension Questionnaire (OHQ) composite score (LS mean difference: -1.2 [95% CI: -2.3, -0.2]). Orthostatic Daily Activities Scale (OHDAS) Item 1 – Standing a short time (LS mean difference: -2.0 [95% CI: -3.6, -0.4])”

P3 data • CNS Disorders • Multiple System Atrophy • Rare Diseases

"$TBPH Ampreloxetine Data in Neurogenic Orthostatic Hypotension to be Presented at the 33rd International Symposium on the Autonomic Nervous System https://t.co/EDvRKBR0s3" (@stock_titan)

Hypotension

Theravance Biopharma to Present New Ampreloxetine Data in Neurogenic Orthostatic Hypotension at the 33rd International Symposium on the Autonomic Nervous System (BioSpace) - “Ampreloxetine (TD-9855) is an...once-daily norepinephrine reuptake inhibitor in development for the treatment of symptomatic neurogenic orthostatic hypotension (nOH) in patients with multiple system atrophy (MSA)….The Company held a Type C meeting with the FDA in June 2022 and agreed on a path to NDA filing with one new Phase 3 clinical study in MSA patients with symptomatic nOH. The Company plans to start the new Phase 3 study in early 2023, with a primary endpoint of Change in OHSA Composite Score.”

New P3 trial • CNS Disorders • Multiple System Atrophy • Rare Diseases

"$TBPH Theravance Biopharma to Present New Ampreloxetine Data in Neurogenic Orthostatic Hypotension at the 33rd International Symposium on the Autonomic Nervous System https://t.co/XyPS1d7KEu" (@stock_titan)

Hypotension

HEPQUANT SHUNT IS SUPERIOR TO CHILD-PUGH IN DEFINING HEPATIC IMPAIRMENT FOR PHARMACOKINETIC STUDIES: EXPERIENCE WITH AMPRELOXETINE (AN ENCORE PRESENTATION) (AASLD 2022) - P1 | "Ampreloxetine AUC inf is increased in subjects with moderate or severe hepatic impairment and correlates strongly with HepQuant DSI and SHUNT%. Use of such quantitative measures of liver function could reduce misclassification of the severity of liver disease and improve upon current classification based on Child-Pugh score. HepQuant DSI (as opposed to CP class) may thus optimize dose recommendations in individual patients and improve the efficacy and safety profile of novel therapeutics for patients with liver disease."

Clinical • PK/PD data • Cardiovascular • Hepatology • Hypertension

Theravance Biopharma, Inc. Reports Second Quarter 2022 Financial Results and Provides Business Update (PRNewswire) - “Ampreloxetine…The Company plans to start the new Phase 3 study in early 2023, with a primary endpoint of Change in OHSA Composite Score. The Company reiterates it expects the $25 million investment from Royalty Pharma to fund the majority of the Phase 3 costs as a result of study size as well as insights and learnings from earlier studies…. Transaction-Related Legal Expenses: Non-routine legal expenses were $3.8 million and $5.1 million for the three and six months ended June 30, 2022, respectively, and were related to the sale of our units in TRC and ampreloxetine investment in July 2022.”

Commercial • New P3 trial • CNS Disorders • Multiple System Atrophy • Rare Diseases

REDWOOD: Phase 3 Clinical Effect Durability of TD-9855 for Treating Symptomatic nOH in Subjects With Primary Autonomic Failure (clinicaltrials.gov) - P3; N=203; Terminated; Sponsor: Theravance Biopharma; Trial completion date: Aug 2022 ➔ Nov 2021; Active, not recruiting ➔ Terminated; Trial primary completion date: Aug 2022 ➔ Nov 2021; Stopped early due to company decision. Company decision based on analysis results in TD-9855-0169.

Clinical • Trial completion date • Trial primary completion date • Trial termination • CNS Disorders • Hypotension • Movement Disorders • Parkinson's Disease • Primary Dysautonomia

Phase 3 Open-Label Extension Study of TD-9855 for Treating Symptomatic nOH in Subjects With Primary Autonomic Failure (clinicaltrials.gov) - P3; N=110; Terminated; Sponsor: Theravance Biopharma; Trial completion date: Dec 2025 ➔ Nov 2021; Active, not recruiting ➔ Terminated; Trial primary completion date: Dec 2025 ➔ Nov 2021; Stopped early due to company decision. Company decision based on analysis results in TD-9855-0169.

Clinical • Trial completion date • Trial primary completion date • Trial termination • Hypotension • Primary Dysautonomia