A second phase 3 study evaluating the efficacy and safety of ampreloxetine for the treatment of adults with symptomatic neurogenic orthostatic hypotension (nOH) did not meet its primary endpoint.

Ampreloxetine is an investigational, long-acting, oral, once-daily norepinephrine reuptake inhibitor. The 22-week, multicenter, randomized withdrawal REDWOOD study (ClinicalTrials.gov Identifier: NCT03829657) evaluated the sustained clinical benefit and safety of ampreloxetine in 154 patients aged 30 years and older with primary autonomic failures (eg, multiple symptom atrophy [MSA], Parkinson disease [PD], pure autonomic failure [PAF]) and symptomatic neurogenic orthostatic hypotension. 

The study included a 16-week open-label period followed by a 6-week double-blind, placebo-controlled, randomized withdrawal period. The primary endpoint of treatment failure was defined as a worsening from baseline in question #1 (dizziness, lightheadedness, feeling faint, or feeling like you might blackout) of the Orthostatic Hypotension Symptom Assessment (OSHA) and Patient Global Impression of Severity (PGI-S) scores by 1.0 point.

Results showed for the overall population, the primary endpoint was not found to be statistically significant (odds ratio, 0.6; P =.196). Overall, patients treated with ampreloxetine had a 40% reduction in the odds of treatment failure compared with placebo.

Subgroup analysis by disease type showed that treatment with ampreloxetine was largely beneficial for MSA patients (n=40), with an odds ratio of 0.28 (95% CI, 0.05-1.22) suggesting a 72% reduction in the odds of treatment failure compared with placebo. Moreover, improvements across multiple endpoints, including OSHA composite, OSHA #1, Orthostatic Hypotension Daily Activities Scale (OHDAS) composite, and Orthostatic Hypotension Questionnaire (OHQ) composite, were observed in MSA patients. This same benefit was not seen in patients with PD or PAF.

As for safety, ampreloxetine was found to be well tolerated; there were no new safety signals identified and no indication of worsening of supine hypertension based on 24-hour monitoring.

“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, CEO, Theravance Biopharma.

Reference

Theravance Biopharma, Inc. announces results from study 0170, a second phase 3 study of ampreloxetine, in patients with symptomatic neurogenic orthostatic hypotension (nOH). News release. Theravance Biopharma, Inc. April 4, 2022. Accessed April 7, 2022. https://investor.theravance.com/news-releases/news-release-details/theravance-biopharma-inc-announces-results-study-0170-second