Theravance Narrows Focus to Multiple System Atrophy Subset Following Mixed Results from the Ampreloxetine Study

An ampreloxetine study revealed mix results which led Theravence to focus on multiple system atrophy.

An ampreloxetine study revealed mixed results which led Theravence to focus on multiple system atrophy.

Theravance Biopharma announced mixed results from a study evaluating the use of ampreloxetine to reduce symptomatic neurogenic orthostatis hypotension (nOH).

The condition often comes alongside disorders such as Parkinson’s disease (PD), multiple system atrophy (MSA), or pure autonomic failure. While the drug did not show improvement in the overall participant population, a subset of patients with MSA met primary endpoints.

Ampreloxetine is a long-acting, orally-dosed norepinephrine reuptake inhibitor. It has multiple potential indications, including fibromyalgia, attention deficit disorder and nOH.

Results from The Study on Ampreloxetine

Study 0170 included 128 participants, each with either Parkinson’s disease, multiple system atrophy or pure autonomic failure. The 22-week long trial treated patients for 16 weeks with the open-label drug, followed by six weeks of placebo-controlled, double-blind investigation.

The primary endpoint was no worsening of the Patient Global Impression of Severity (PGI-S) or Orthostatic Hypotension Symptom Assessment Scale (OSHA) question No. 1. The latter is a scaled question, rating feelings of dizziness, lightheadedness, feeling faint or feeling an oncoming blackout.

Odds ratio statistical analysis of the results showed that, within the MSA subgroup, a 72% reduction in the odds of treatment failure was seen. This is in contrast to the overall participant improvement, which demonstrated a 40% reduction in the odds of treatment failure. All statistics stand against placebo treatment odds. Theravance will now refocus efforts toward treating MSA patients.

"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 Theravance CEO Rick E. Winningham in response to the results. 

Symptomatic nOH, the focal point of Study 0170, is characterized as a rare disorder that causes a patient’s systolic blood pressure to rapidly drop within three minutes upon standing. Dizziness, fatigue, and other symptoms follow the autonomic system failure. The disorder is often attributed to overarching medical ailments.

“There is an urgency to treat MSA patients suffering with nOH due to the impact on quality of life and the extreme caregiver burden,” commented Roy Freeman, MBChB, professor of neurology and director of the center for autonomic and peripheral nerve disorders at Beth Israel Deaconess Medical Center. “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.” Freeman assisted in the design and interpretation of the study.

According to the National Institute of Neurological Disorders and Stroke, MSA affects the autonomic nervous system and a patient’s mobility, sometimes mirroring symptoms of Parkinson’s disease. It is considered rare, as it is currently a diagnosis carried by 15,000 to 50,000 Americans.

Theravance primarily develops respiratory therapeutics for acute care patients. Much promise lies in nezulcitinib, which has shown mortality rate improvement for patients with COVID-19 related acute lung injury. Additionally, Vibativ (telavancin) was granted New Drug Application (NDA) approval by the U.S. Food and Drug Administration in 2018. Telavancin is an antibiotic aimed at complex infection.

Rather than continue research into other realms, the company announced a decision to become specialized in 2021. A Phase II Study 0157 (NCT03758443) and Phase III Study 0170 (NCT03829657), respectively evaluating izencitinib, a gut-selective JAK inhibitor, as a treatment for Crohn’s disease and ampreloxetine for treating primary autonomic failure, have been terminated.

In September, Theravance was dealt another clinical blow a first Phase III trial investigating ampreloxetine against nOH failed to meet a primary endpoint. To cut expenses, the difficult decision was made to let go of 270 employees, equivalent to 75% of the overall workforce. Fifty employees were also let go following Theravance’s sale of telavancin to Cumberland Pharmaceuticals.

With a renewed focus, Theravance hopes to strategically invest in respiratory therapeutics and regain strong footing in the pharmaceutical industry.

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