Theravance Biopharma Completes Enrollment in Phase 3 CYPRESS Study for Ampreloxetine Treatment

Theravance Biopharma has completed enrollment in its Phase 3 CYPRESS study for ampreloxetine, a potential treatment for symptomatic neurogenic orthostatic hypotension due to multiple system atrophy. The study aims to address the unmet need for effective treatments, with topline results expected in Q1 2026. If successful, ampreloxetine could become the first therapy to provide durable benefits for the estimated 40,000 U.S. patients with MSA-related nOH.

Theravance Biopharma, Inc. has successfully completed enrollment in its pivotal Phase 3 CYPRESS study for ampreloxetine, an investigational therapy aimed at treating symptomatic neurogenic orthostatic hypotension (nOH) in patients with multiple system atrophy (MSA). The study, which focuses on addressing the unmet need for effective treatments, is expected to report topline results in the first quarter of 2026.

The CYPRESS study (NCT05696717) is a global, randomized-withdrawal trial designed specifically for the MSA population. It enrolled patients in the 12-week open-label portion of the study at sites across four continents. The study aims to evaluate the efficacy and durability of ampreloxetine in participants with MSA and symptomatic nOH. If successful, ampreloxetine could become the first therapy to provide durable benefits for the estimated 40,000 U.S. patients with MSA-related nOH.

Dr. Horacio Kaufmann, a member of the advisory committee supporting the CYPRESS clinical trial and a paid consultant to Theravance Biopharma, expressed optimism about the potential of ampreloxetine. "nOH is one of the most debilitating manifestations of MSA, which affects about 40,000 patients in the U.S. alone. Yet current therapies often fail to provide lasting symptom relief, require frequent dosing, and carry a boxed warning for supine hypertension. Ampreloxetine is designed to address the underlying cause of nOH. In Study 0170, it showed compelling improvement in OHSA composite score without worsening supine hypertension," said Dr. Kaufmann.

The study's primary endpoint is the change in the Orthostatic Hypotension Symptom Assessment (OHSA) composite score from randomized-withdrawal baseline to Week 8. Secondary outcome measures include changes from baseline in the Orthostatic Hypotension Daily Activity Scale (OHDAS) items 1 and 3. Theravance Biopharma is preparing for an expedited NDA submission following the results and plans to request priority FDA review if the data are supportive.

Theravance Biopharma has been granted an Orphan Drug Designation for ampreloxetine for the treatment of symptomatic nOH in patients with MSA. The company is committed to advancing high-impact catalysts and delivering on its strategic focus to bring transformative therapies to underserved patient populations.

References:
[1] https://www.marketscreener.com/news/theravance-biopharma-inc-completes-enrollment-in-pivotal-phase-3-cypress-study-of-ampreloxetine-in-ce7c50d8d98bf122
[2] https://www.morningstar.com/news/pr-newswire/20250825sf57834/theravance-biopharma-completes-enrollment-in-pivotal-phase-3-cypress-study-of-ampreloxetine-in-patients-with-symptomatic-neurogenic-orthostatic-hypotension-due-to-multiple-system-atrophy