Abstract Details

Title Preclinical Development of a Novel Precision Olfactory Delivery (POD®) - L-dopa Drug-Device Combination Product for the Treatment of OFF Episodes in Parkinson’s Disease

Topic Movement Disorders

Presentation(s) P2 - Poster Session 2 (5:30 PM-6:30 PM)

Poster/Presentation
Number 10-049

Objective Impel NeuroPharma has developed the POD device to generate rapid, consistent systemic levels of drugs for neurological diseases. This work was to develop a L-dopa powder formulation delivered by the POD device that results in plasma exposure in rats and non-human primates (NHP), that when extrapolated to humans, will be sufficient to reverse OFF episodes in Parkinson’s disease (PD) patients.

Background L-dopa has been the “platinum” standard PD treatment for over 50 years^1,2. As PD advances, patient response to pharmacotherapy decreases; the benefits of L-dopa become increasingly sensitive to change in systemic concentrations resulting in motor fluctuations (OFF episodes)³. Previous studies report the L-dopa plasma concentration threshold for switching from OFF to ON is approximately 400 ng/mL⁴. POD-L-dopa is a drug-device combination product consisting of a novel L-dopa powder formulation delivered to the upper nasal cavity by the POD device.

Design/Methods Powder L-dopa formulations were designed and manufactured for POD device delivery and evaluated by analytical methods including assay, related substances, X-ray diffraction, differential scanning calorimetry, and device compatibility. Lead formulations were evaluated in rat and NHP using species specific POD devices.

Results Over 50 formulations were manufactured, and 30 formulations were assessed in vivo. PK assessment focused on comparing time to achieve 400 ng/mL plasma levodopa, T_max, and C_max. Lead formulation candidates resulted in concentrations of 400 ng/mL within 5 - 12 min in NHP, a 3 to 5-fold improvement compared to unformulated L-dopa. Median T_max occurred between 30-60 min with C_max values exceeding 1 µg/mL.

Conclusions Impel is developing POD-L-dopa, a powder formulation of L-dopa delivered to the vascular-rich upper nasal cavity with the POD device, allowing self- or care-giver administration, to achieve consistent and rapidly effective treatment to abort OFF episodes. This work has led to the selection and further evaluation of a novel formulation in a Phase 2A clinical study.

Authors/Disclosures
Kelsey Satterly PRESENTER	Kelsey Satterly has received personal compensation for serving as an employee of Impel NeuroPharma . Kelsey Satterly has received intellectual property interests from a discovery or technology relating to health care.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Hong Lin, PhD (Children'S Hospital of Philadelphia)	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Stephen B. Shrewsbury, MD (Impel Pharmaceuticals)	Dr. Shrewsbury has received personal compensation for serving as an employee of Impel NeuroPharma. Dr. Shrewsbury has received stock or an ownership interest from Impel NeuroPharma.
	No disclosure on file

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