Review identifies 132 areas of impact, including quality of life and fatigue
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A comprehensive review of the scientific literature identified more than 100 distinct ways in which off episodes affect people with Parkinson’s disease, highlighting a multifaceted burden that extends beyond movement symptoms to include cognitive, emotional, and quality-of-life impacts.
The research was presented by Merz Therapeutics, the company that markets Inbrija (levodopa inhalation powder), at the World Parkinson Congress 2026, held last month in Phoenix.
The findings showed that often overlooked nonmotor symptoms such as fatigue, memory difficulties, and anxiety can be as disruptive as physical symptoms during off episodes — periods when symptoms return in between medication doses — underscoring the need for treatment approaches that address the full patient experience.
The company also presented additional analysis from three Phase 3 trials confirming the safety and efficacy of Inbrija (levodopa inhalation powder) in providing consistent and rapid motor improvement for patients experiencing off episodes.
“For too long, the conversation around ‘off’ episodes has focused primarily on visible motor symptoms. Our research highlights what we’ve been hearing from people with Parkinson’s: the burden of an ‘off’ episode is far broader and more disruptive than what can be seen,” Stefan Albrecht, MD, PhD, Merz’s chief scientific and medical officer, said in a company press release. “It is a call to action for the entire Parkinson’s community to recognize and address the significant impact of ‘off’ episodes.”
Parkinson’s is caused by the progressive loss of dopaminergic neurons, the nerve cells that produce dopamine, a signaling molecule involved in motor control. This leads to both motor symptoms, such as tremors, rigidity, and slowed movements, and nonmotor symptoms, including cognitive and emotional changes, mental issues, and sleeping problems.
Levodopa, a molecule that can be converted into dopamine, is the mainstay treatment for easing the disease’s motor symptoms. However, its long-term use may cause off episodes, which are more frequent and severe as the disease progresses. These episodes can be unpredictable and impact a person’s ability to perform daily activities.
Inbrija is an inhaled levodopa formulation approved to ease Parkinson’s symptoms during off episodes. It delivers a precise dose directly to the lungs, where it can rapidly enter the bloodstream and reach the brain to stabilize symptoms.
Researchers found that off episodes can affect patients in 132 different ways, encompassing not only movement-related difficulties but also fatigue, anxiety, memory problems, and other factors that can impair quality of life.
Additionally, data pooled from three Phase 3 trials involving 437 people with Parkinson’s disease confirmed that Inbrija provides rapid motor benefit during off episodes. Patients treated with Inbrija experienced a significant improvement in Unified Parkinson’s Disease Rating Scale Part 3 scores, reflecting reduced motor symptom severity.
In particular, patients who had been experiencing off episodes for less than two years before starting Inbrija saw a mean reduction of 14.3 points, while those with a longer history of off episodes (two years or more) experienced a similar 14.8-point decrease.
Safety analyses also confirmed Inbrija’s favorable tolerability profile, with predominantly mild treatment-emergent adverse events, most commonly cough and throat irritation. The estimated probability of remaining free of treatment-related cough after more than a year was 84.7%.
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