#United States #San Diego #Theravance Biopharma #Ampreloxetine #nOH

Theravance Biopharma to Present Groundbreaking Findings at the AAN Meeting

Theravance Biopharma, Inc. has revealed its plans to present key analyses from the Phase 3 trials of ampreloxetine at the 77th Annual Meeting of the American Academy of Neurology (AAN). This event is scheduled to take place from April 5-9, 2025, in the vibrant city of San Diego, California. The presentation will focus on the selective pharmacodynamic profile of ampreloxetine, particularly concerning its effectiveness in treating symptomatic neurogenic orthostatic hypotension (nOH) in patients suffering from multiple system atrophy (MSA).

The preliminary studies of ampreloxetine, identified as Studies 169 and 170, pave the way for deeper exploration into treating nOH. The results from these studies have prompted the activation of the CYPRESS Study 197, a further investigation into the therapeutic potential of ampreloxetine for patients diagnosed with nOH linked to multiple system atrophy, currently underway.

Presentation Schedule

The scheduled analyses will occur sequentially during a platform session on April 7, 2025. The presentations will include two pivotal studies:
1. Iodice V, et al. - Exploring NET-Inhibition with Ampreloxetine, Blood Pressure, and Catecholamines in nOH patients (Program Number S9.001)
2. Norcliffe-Kaufmann L, et al. - Assessing Ampreloxetine's Impact on Supine Hypertension through an Ambulatory Blood Pressure Monitoring Study (Program Number S9.002)

Insights into Ampreloxetine

Ampreloxetine is an investigational norepinephrine reuptake inhibitor designed for once-daily use. Targeting symptomatic nOH, this therapy shows promise for enhancing norepinephrine levels and maintaining stable blood pressure, contributing to significant and sustained symptom relief among MSA patients. Notably, there is no associated risk of exacerbating supine hypertension, which is a crucial advantage for many affected individuals.

In the United States, ampreloxetine holds an Orphan Drug Designation aimed at addressing the challenges posed by symptomatic nOH in MSA patients. Theravance Biopharma is gearing up to file a New Drug Application (NDA) pending favorable outcomes from the ongoing Phase 3 CYPRESS study.

The CYPRESS Study Overview

The CYPRESS Study (NCT05696717) is a Phase 3 registrational trial that is actively enrolling participants. This multi-center study focuses on evaluating the efficacy and long-term benefits of ampreloxetine in patients suffering from MSA and symptomatic nOH after 20 weeks of treatment.
The study is structured in four main phases:
1. Screening Period
2. Open Label Period (12 weeks, where participants receive a daily dose of 10 mg ampreloxetine)
3. Randomized Withdrawal Phase (8 weeks, double-blind placebo-controlled)
4. Long-term Treatment Phase

The primary objective is to measure changes in the Orthostatic Hypotension Symptom Assessment (OHSA) composite score. Additionally, secondary assessments focus on the Orthostatic Hypotension Daily Activity Scale (OHDAS), which evaluates various activities requiring standing or walking.

Previous Phase 3 Findings

Research conducted in Study 0170 focused on treatment outcomes for symptomatic nOH and involved a comprehensive 22-week approach, integrating both an open-label and a double-blind random withdrawal phase. Even though the primary endpoint was not met for the overall population, an enlightening subgroup analysis highlighted substantial benefits among MSA patients, showing a 72% reduction in treatment failure odds when using ampreloxetine versus placebo (Odds Ratio: 0.28).

Understanding MSA and nOH

Multiple System Atrophy (MSA) is a progressive neurological condition affecting motor control and autonomic functions. A key symptom, neurogenic orthostatic hypotension (nOH), leads to drastic blood pressure drops upon standing, severely impacting the patient’s quality of life. Studies suggest around 70-90% of MSA patients experience nOH symptoms, with an estimated 50,000 diagnosed individuals in the U.S. alone.

Theravance Biopharma’s Mission

Theravance Biopharma is dedicated to creating innovative medications that significantly improve patients' lives. With the development of FDA-approved treatments such as YUPELRI® for chronic obstructive pulmonary disease (COPD), the company is now setting its sights on ampreloxetine. This therapy could be revolutionary for MSA patients struggling with chronic, debilitating symptoms of nOH. As they prepare to unveil their findings at the AAN meeting, Theravance is committed to advancing research that may lead to new hope for patients and families affected by this complex condition.

Through its commitment to scientific excellence and patient care, Theravance Biopharma continues to drive its mission of delivering impactful solutions in the realm of neurological disorders.