Theravance Biopharma’s late-stage failure suddenly became a jump-off point for treating multiple system atrophy (MSA) according to a recently published article in Neurology Live. After the failure of two drugs which included a four-week study of ampreloxetine, Theravance cut 75% of its staff.
But the remaining group revisited the initial study focusing on a certain group of patients. While ampreloxetine failed to achieve its intended results, it showed surprising improvements against symptoms experienced by MSA patients with neurogenic orthostatic hypotension. Theravance rushed its findings (NCT03829657) to the FDA. It then proposed a trial with ampreloxetine for MSA patients.
Dr. Roy Freeman, a neurology professor at Beth Israel, noted that ampreloxetine has the potential to improve critically important symptoms related to the control of blood pressure. He further stated that it has the potential as a therapy for MSA patients.
About MSA
MSA affects approximately 75,000 people in the U.S. It is a neurological disorder that impacts such functions as digestion, blood pressure, and heart rate. MSA mimics Parkinson’s disease in its early stages. It attacks nerve cells in the brain and spinal cord resulting in the loss of muscle coordination, tremors, and speech difficulties.
Symptoms of MSA generally emerge in mid-life but progress rapidly in the next ten years leading to cardiac or respiratory arrest.
Currently, there is no approved treatment. The urgency to find treatment and a cure is the result of the impact of MSA on patients and the heavy burden on caregivers.
Patients receiving ampreloxetine, an oral, long-acting, once-daily norepinephrine reuptake inhibitor, showed a 40% reduction in the risk of treatment failure compared to a placebo. MSA patients received the largest benefit among the subgroups.
Neurogenic Orthostatic Hypotension (nOH)
The disease nOH is present in approximately eighty percent of MSA patients. It is a rare disorder that is caused by low blood pressure that occurs by impaired activation of sympathetic neurons.
Encouraging Results
After taking ampreloxetine as prescribed, clinicians found a 72% reduction in the risk of treatment failure. MSA patients were able to stand and walk for short periods. According to the company, there was no indication of any new safety signals or elevation in blood pressure due to changing positions.
The nerves of MSA patients are found to be more intact and provide better models for treatment with the drug. Theravance has been especially proactive in its effort to inform the FDA of ampretoxetine’s potential impact on MSA.
About Treatment-Emergent Adverse Events (AEs)
53% of the 103 patients examined after a sixteen-week open-label period experienced AEs that were mild to moderate. Eight percent (n-16) reported AEs that were serious with five deaths. However, the AEs and deaths were not related to ampreloxetine.
Furthermore, in a six-week double-blind withdrawal period four serious AEs were reported in the ampreloxetine group with two of the incidents related to the investigational agent. Two deaths were recorded with one unrelated to ampreloxetine. The second was recorded as unknown but inferred as being related. One of two serious AEs was reported in the placebo group with one reported to be related to the study drug.
Dr. Rick Winningham, CEO of Theravance, stated that the company is interacting with health authorities to find a path forward toward expediting ampreloxetine for the treatment of MSA.
