Ampreloxetine May Improve Neurogenic Orthostatic Hypotension Symptoms in Multisystem Atrophy

In the phase 3 Study 0170 (NCT03829657) treatment with ampreloxetine (TD-9855; Theravance Biopharma, Cayman Islands) vs placebo was 40% more likely to reduce symptoms of neurogenic orthostatic hypotension (nOH). Individuals in the study (n=128 out of n=154 planned) had nOH as a result of Parkinson disease (PD), pure autonomic failure (PAF), or MSA. In the overall population, the likelihood of symptom reduction was not statistically significant; however, in prespecified subpopulation analysis, benefits of ampreloxetine in participants with MSA were significantly higher (72%; 95%CI, 0.05-1.22). 

"MSA is a devastating and debilitating disease with no effective disease modifying treatment. There is an urgency to treat MSA patients suffering with nOH due to the impact on quality of life and the extreme caregiver burden. Ampreloxetine appears to improve a narrow, but critically important group of symptoms related to blood pressure control, and along with the safety profile, may represent a potential therapy for MSA patients," said Roy Freeman, MBChB, Professor of Neurology, Director, Center for Autonomic and Peripheral Nerve Disorders, Beth Israel Deaconess Medical Center, who assisted in the design and interpretation of the study.

"At Theravance Biopharma, we are guided by patient outcomes. Given the clear unmet need for MSA patients suffering from symptomatic nOH, we are engaging potential partners and planning health authority interactions to determine a path forward in hopes of expediting ampreloxetine as a possible treatment option for people with MSA," said Rick E Winningham, Chief Executive Officer, Theravance Biopharma.

Participants in this withdrawal study were treated with ampreloxetine or placebo for a 16-weeks open-label period followed by a 6-week double-blind period in which participants were randomly assigned to continue ampreloxetine or receive placebo. nOH symptoms were measured with the Orthostatic Hypotension Symptom Assessment Scale (OHSA) question #1 and Patient Global Impression of Severity (PGI-S) scores. 

No worsening of supine hypertension was observed using 24-hour monitoring and ampreloxetine was well-tolerated with no new safety signals seen.