Current and novel infusion therapies for patients with Parkinson's disease

Abstract

Advanced Parkinson's disease is characterized by periods of poor mobility, dyskinesia and progressive decline in functional independence of the affected person despite the manipulation of levodopa doses and the introduction of supplemental therapies such as catechol-O-methyl transferase inhibitors, monoamine oxidase-B inhibitors and dopamine agonists. The implementation of drug delivery systems allows to bypass problems related to irregular and often unpredictable intestinal absorption of oral levodopa, which significantly affects its bioavailability and contributes to the development and persistence of motor complications. Subcutaneous apomorphine and levodopa/carbidopa jejunal infusion systems have been available for many years and their efficacy is confirmed by randomized studies and long-term experience in many centers worldwide. Recently, a new formulation of levodopa/carbidopa infusion gel that includes the catechol-O-methyl transferase inhibitor Entacapone has been introduced to the market. The use of entacapone allows to reduce total daily dose of administered levodopa. Two different soluble formulations of levodopa/carbidopa (ND0612 and ABBV-951) have completed clinical development, and both can ensure subcutaneous delivery by a portable pump infusion system. ABBV-951 uses a foslevodopa/foscarbidopa formulation, both prodrugs to improve absorption and tolerability. Both systems provide effective improvement of motor complications and are likely to expand the therapeutic options in advanced patients. Future efforts should focus on the earlier detection of patients who are candidates for device-aided therapies, increasing appropriate referral and broadening the availability of these treatments globally.

Keywords: Apomorphine; Device-aided therapies; Infusion therapies; Levodopa/carbidopa intestinal gel; Parkinson’s disease; Subcutaneous levodopa.

Fig. 1

Overview of currently available and upcoming infusion systems in Parkinson’s disease

Fig. 2

Changes in the duration of ON and OFF time (in hours) from different infusion therapies with respect to the baseline scores. *Poewe et al. ; **Soileau et al. ; °Katzenschlager et al. ; °°Olanow et al. . *This study was not randomized and open-label but results were confirmed by the BouNDless study (in press)