An experimental drug that Theravance Biopharma touted as a potential first-in-class medicine for multiple system atrophy has failed a Phase 3 study, triggering a corporate shakeup that ends this program and the company’s R&D, leading to the layoff of about 50% of employees.
In connection with the restructuring, Dublin-based Theravance said Tuesday that a committee comprised of members of its board of directors is reviewing strategic alternatives that could include a sale of the company.
The Theravance drug, ampreloxetine, was being tested as a treatment for neurogenic orthostatic hypotension (nOH) in patients with multiple system atrophy (MSA). This rare neurodegenerative disorder affects the central nervous system as well as the autonomic nervous system, which controls involuntary functions such as blood pressure. Many MSA patients experience nOH, in which autonomic nervous system dysfunction impairs blood pressure regulation.
MSA has no cure and treatment consists of drugs used off label to address disease symptoms. Ampreloxetine is a small molecule norepinephrine reuptake inhibitor. Blocking this target was intended to lead to an increase in extracellular concentrations of norepinephrine, a neurotransmitter that increases and maintains blood pressure. The main goal of ampreloxetine’s placebo-controlled pivotal test was to measure at week 8 the change in score according to a scale used to assess hypotension symptoms.
Without releasing specific figures, Theravance said the Phase 3 results were not statistically significant. The company said the study drug was generally well tolerated with safety findings consistent with prior studies. Though the ampreloxetine program will be wound down, Theravance said it will complete analysis of the Phase 3 results, and in consultation with outside experts, assess whether the data merit further discussion with regulators. The company added that this assessment is intended to provide the board committee “with additional clarity regarding any remaining value in ampreloxetine for Theravance shareholders.”
Ampreloxetine’s MSA failure is the latest in a string of disappointing clinical trial outcomes for the drug. In 2021, the drug failed a four-week placebo-controlled study that enrolled patients with Parkinson’s disease, pure autonomic failure, and MSA with symptomatic nOH.
The drug was also evaluated in a separate open-label study. About 40% of participants enrolled had MSA based on the hypothesis that ampreloxetine would work best in these patients because they have more intact nerves on which the study drug can exert its effect, Theravance said in its annual report. While results reported in 2022 were not statistically significant in the overall study population, a subgroup analysis suggested benefit in MSA patients.
Following discussions with the FDA, the agency agreed that one additional Phase 3 test in MSA patients with symptomatic nOH could support an application seeking regulatory approval in this patient population. That study began in 2023. In the runup to the expected trial readout, Theravance held an investor event this past December, during which executives said ampreloxetine offered blockbuster sales potential and could become a new standard of care for nOH in MSA patients.
With the restructuring, Theravance said it will streamline costs and align its focus to Yupelri, a chronic obstructive pulmonary disease (COPD) drug that is marketed by partner Viatris. Theravance also receives revenue in the form milestone payments tied to sales of GSK’s COPD and asthma drug Trelegy. In 2022, Theravance sold its economic interest in the asset to Royalty Pharma for about $1.11 billion in upfront cash and milestone payments tied to sales of the drug. Theravance said it expects the restructuring will reduce operating expenses by about 60%, leading to savings of about $70 million.
“With a profitable commercial product, an expected cash balance of approximately $400 million at the end of the first quarter of 2026, and the anticipated $100 million Trelegy milestone in 2026, we continue to have a strong set of assets,” Theravance CEO Rick Winningham said in a prepared statement.
Photo: Martin Barraud, Getty Images
