Regulatory Case Study: A Strategic Abuse Potential Assessment of Acorda Therapeutics’ INBRIJA™ (levodopa inhalation powder)

Categories: Abuse Potential Assessment, Scheduling

By Reggie Fant

In December 2018, the Food and Drug Administration (FDA) approved Acorda Therapeutics’ INBRIJA, the first levodopa inhalation powder for the intermittent treatment of OFF episodes in people with Parkinson’s disease treated with carbidopa/levodopa. As Parkinson’s disease progresses, many people with Parkinson’s fluctuate between ON periods, during which symptoms are controlled and OFF episodes, also known as OFF periods, which are the return of Parkinson’s symptoms that result from low levels of dopamine between doses of treatment.

PinneyAssociates helped Acorda Therapeutics prepare the scientific and public health rationale to support the position that INBRIJA should not be placed into a schedule under the United States Controlled Substances Act (CSA).

Parkinson’s disease is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the brain.  Levodopa, a metabolic precursor of dopamine, increases intracellular dopamine levels in the brain of Parkinson’s patients.

As with all treatments that act on the central nervous system, the FDA required evaluation of abuse potential as per the 2017 Guidance for Industry, Assessment of Abuse Potential of Drugs. For the NDA submission of INBRIJA, Acorda Therapeutics needed an evaluation of the abuse potential of their inhalation powder formulation relative to a marketed oral formulation (none of which are scheduled) to demonstrate that the inhalational route of administration did not increase the likelihood that INBRIJA would be abused or diverted. Scientific evidence was necessary for the FDA to determine that placement into a schedule under the United States (U.S.) Controlled Substances Act was not required.

Our Approach

PinneyAssociates scientists and regulatory experts utilized the full depth and breadth of the available science on the abuse potential of levodopa to address FDA requirements and provided scientific evidence and a public health rationale that INBRIJA should not be placed into a schedule.  This included:

  • A comprehensive review of the pharmacology of levodopa
  • An extensive strategic review of the literature related to nonmedical use, misuse, and abuse of and withdrawal associated with levodopa
  • Assessment of federal survey data about nonmedical use or abuse of levodopa
  • A pharmacokinetics comparison of the inhalation formulation to currently marketed oral formulations of levodopa
  • Independent assessment of clinical trial data including adverse events possibly related to abuse potential or withdrawal, and drug accountability
  • Consideration of the public health impact including likely benefits and risks of the product
  • Development of an abuse potential assessment of the formulation, and a recommendation for no scheduling, which were submitted as part of the NDA
  • Assistance in preparing for the pre-NDA meeting, and review of data analyses in support of interactions with the FDA

Value to Acorda

The abuse potential assessment and scheduling recommendation developed by PinneyAssociates contributed to the FDA’s determination that INBRIJA did not warrant placement into a schedule of the Controlled Substances Act.