Theravance Biopharma Inc. has just released results from their 2nd Phase 3 investigation of Ampreloxetine as a therapy for symptomatic neurogenic orthostatic hypotension (nOH).

Symptomatic nOH

NOH is a rare condition which leads to a sustained drop in systolic Bp of 20mm HG or less, or a diastolic Bp of 10mm Hg or less. This drop occurs in the first 3 minutes of being in a standing position. The condition is the result of a malfunction in the autonomic nervous system. It is associated with a few underlying conditions such as Parkinson’s disease (PD), pure autonomic failure (PAF), and multiple system atrophy (MSA).

Some patients who have a severe form nOH can’t stand for more than a couple of seconds. The drastic drop in blood pressure causes dizziness, fatigue, fainting, weakness, neck pain, blurry vision, and trouble concentrating.

Ampreloxetine

Ampreloxetine, or TD-9855, is an investigative oral medication taken once a day. It is long-acting and potent. The therapy is a type of norepinephrine reuptake inhibitor.

This therapy has already been studied as a treatment for ADHD and fibromyalgia in more than 800 patients.

Study 0170

Study 0170 was a Phase 3 investigation studying Ampeloxetine as a treatment for nOH. It was a 22 week investigation which included a 16 week open label study and then  a six week randomized and placebo-controlled withdrawal period.

This trial’s primary endpoint was the treatment failing at the six week mark. This failure was assessed by using the first question from the Orthostatic Hypotension Symptom Assessment Scale (OHSA), as well as changes in the Patient Global Impression of Severity scores.

The research team found that the primary endpoint was not statistically significant for PD, PAF, and MSA patients. This finding demonstrates that ampreloxetine treatment reduces the chances of treatment failure by 40% compared to a placebo.

The team then specifically studied results by disease subtype. They uncovered that the findings were largely the result of MSA patients. For this population, the treatment had a 72% reduction in the chances of treatment failure.  For the patients who withdrew to placebo, a decrease in blood pressure while standing was documented. For those who maintained the ampreloxetine treatment, no clinically relevant decrease was documented.

The company is now working to investigate why this effect was not found in individuals with PAF or PD. Importantly, the therapy was found to be well tolerated. Additionally, no further safety concerns were noted in this trial.

You can read more about this Phase 3 investigation and its findings here.