Acorda's Inhaled Levodopa Effective Regardless of Food Intake

Recent data presented at the 3^rd Annual Pan American Parkinson’s Disease and Movement Disorders Congress (MDS-PAS) compare the pharmacokinetic profile of inhaled levodopa (Inbrija; Acorda Therapeutics) with oral carbidopa/levodopa (CD/LD) after a meal. The data suggest that the treatment can be used regardless of food intake, and with rapid effect in patients with Parkinson disease.

As the effect of food and delayed gastric emptying can contribute to the unpredictability of levodopa levels in the blood after oral dosing, these data suggest promise for inhaled levodopa. To find out more about the data and what they mean for physicians, NeurologyLive spoke with Holly Roberts, MD, executive medical director, Medical Affairs/Clinical Development, Acorda Therapeutics.

NeurologyLive: What prompted this work with inhaled levodopa?

Holly Roberts, MD: Oral levodopa is the most effective treatment for the management of Parkinson’s motor symptoms. But its use can be complicated by a shortening of the duration of effect for each dose over time, resulting in periods of inadequate responsiveness. This inadequate responsiveness is hallmarked by the return of Parkinson’s symptoms, commonly called OFF periods.

OFF periods may occur unpredictably, partly because of the pharmacokinetic variability of baseline therapy (oral levodopa) due to gastrointestinal (GI) dysfunction characteristic of Parkinson’s and food effects that impact absorption.

Inbrija (levodopa inhalation powder), which was approved by the FDA in December 2018, offers systemic delivery of levodopa via the pulmonary route, entering the bloodstream through the lungs and then traveling to the brain. It does not depend on absorption through the digestive tract.

The pharmacokinetic profile study presented at MDS-PAS 2020 aimed to evaluate the food effect on Inbrija and oral CD/LD in people with Parkinson’s in the fed state, which was not previously studied.

What is the key takeaway for the clinical community?

This study showed that in people with Parkinson’s, following a meal high in fat and protein, Inbrija increased levodopa levels in the blood more quickly and with less variability than with oral carbidopa/levodopa (CD/LD).

Specifically, this study found:

• Following a single inhaled dose of Inbrija 84 mg in the fed condition, plasma levodopa concentrations increased to maximum observed plasma concentration (T_max) in a median time of 15 minutes post-dose. After CD/LD dosing, plasma concentrations did not substantially increase for approximately 1 hour and median T_max occurred at 120 minutes.
• 10 minutes after dosing, plasma levodopa levels with Inbrija were about twice that with oral CD/LD, and after 30 minutes they were about 75 percent greater.
• Plasma levodopa profiles of individual subjects exhibited less variability after Inbrija inhalation than after oral CD/LD dosing.
• Inbrija can be used without regard to food intake, and Inbrija administration to patients with Parkinson’s under fed conditions was safe and well-tolerated in this study.

Do these data have any potential implications for prescribing best practices?

These differences between oral CD/LD and Inbrija pk profile reveal the food effect for oral CD/LD in the gastrointestinal tract in patients with PD.

These data support the utilization of Inbrija irrespective of meals and suggest Inbrija may be of benefit in patients who manifest delayed gastric emptying as a manifestation of PD and for those with postprandial delays in symptom control after oral CD/LD dosing.

Transcript edited for clarity.