Theravance Completes Enrollment in Phase 3 CYPRESS Trial for MSA Patients with nOH

Theravance Completes Enrollment in Phase 3 CYPRESS Trial for MSA Patients with nOH

By, Admin 27 August 2025

Neurogenic orthostatic hypotension (nOH) is one of the most debilitating symptoms of multiple system atrophy (MSA). Patients face sudden drops in blood pressure when standing.

Why This Matters

Roughly 80% of MSA patients experience nOH. Symptoms include dizziness, fainting, and blurry vision. These episodes can cause falls, disability, and severe loss of independence.

Despite the seriousness, there are limited effective treatments designed specifically for MSA-related nOH. Current options often provide only short-term relief, require frequent dosing, and carry safety concerns.

The Promise of Ampreloxetine

Ampreloxetine, a once-daily selective norepinephrine reuptake inhibitor, is being investigated as a treatment targeting the root cause of nOH in MSA patients.

Dr. Horacio Kaufmann from NYU Grossman School of Medicine explained:

“Ampreloxetine showed compelling improvement in OHSA scores without worsening supine hypertension. If confirmed, I’d use it in most of my MSA patients.”

Inside the CYPRESS Study

  • Study Type: Global, phase 3, randomized-withdrawal trial.
  • Patient Base: Symptomatic nOH due to clinically diagnosed MSA.
  • Design: Patients received 12 weeks of open-label ampreloxetine, then responders were randomized to continue treatment or switch to placebo for eight weeks.
  • Primary Endpoint: Change in Orthostatic Hypotension Symptom Assessment (OHSA) composite score from baseline to Week 8.

Áine Miller, Head of Development at Theravance, emphasized:

“Completing enrollment is a major step toward bringing a transformative therapy to underserved MSA patients. CYPRESS builds on insights from Study 0170 and robust execution.”

Timeline and Next Steps

Theravance expects topline CYPRESS data in Q1 2026. The company is preparing for an expedited NDA submission and may seek priority FDA review, pending results.

Ampreloxetine has already received Orphan Drug Designation in the US for nOH in MSA patients.

Prior Studies That Shaped CYPRESS

  • Study 0169: A phase 3 trial (n=195) that did not meet its primary endpoint across all patients, including those with Parkinson’s and pure autonomic failure.
  • Study 0170: A 22-week trial showed that ampreloxetine benefits were strongest in MSA patients, with multiple endpoints favoring treatment over placebo.

For MSA patients, ampreloxetine demonstrated:

  • Increased norepinephrine levels.
  • Favorable impact on blood pressure.
  • Durable symptom improvement.
  • No worsening of supine hypertension.

The Patient Context

MSA affects approximately 50,000 people in the US. Between 70–90% experience nOH symptoms. Severe cases make standing nearly impossible, triggering cerebral hypoperfusion and syncope.

Symptoms include: dizziness, fainting, fatigue, weakness, blurry vision, poor concentration, and head or neck pain. These drastically reduce daily independence and quality of life.

Theravance’s Bigger Mission

Theravance Biopharma positions itself as a company delivering “Medicines that Make a Difference.” Its track record includes the FDA-approved Yupelri (revefenacin) for COPD maintenance therapy.

The company believes ampreloxetine could become a new standard for treating nOH in MSA — if CYPRESS confirms its potential.

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