At the American Academy of Neurology (AAN) 2023 Annual Meeting, data on AbbVie’s ABBV-951 (foslevodopa/foscarbidopa) and NeuroDerm’s ND0612 (levodopa/carbidopa) were showcased for the treatment of Parkinson’s disease (PD). Should they receive FDA approval, these innovative levodopa delivery systems could offer an improved route of administration and will create additional options to control various motor complications in patients with advanced-stage PD. However, patient and physician education is important to improve patient outcomes.
Innovation in drug formulations and delivery systems is one of the most rapidly changing areas in PD treatment. This is mostly driven by the market for the need for the steady levodopa plasma concentration to control PD motor symptoms and avoid dyskinesia and off-episodes. AbbVie’s Duopa/Duodopa, a levodopa continuous-release intestinal pump, is sometimes offered to advanced-stage patients to achieve constant blood levels of levodopa. However, key opinion leaders (KOLs) previously interviewed by GlobalData noted that this option is invasive, as it requires a surgical procedure to insert a permanent tube through endoscopic gastrostomy, and an external portable pump is used to administer levodopa gel. Furthermore, the burden of carrying the pumping apparatus required for Duodopa treatment often can cause severe discomfort for patients. If approved, ABBV-951 and ND0612 are expected to be an improvement to the Duodopa device as they are smaller, and a surgical procedure is not required to install them.
At the AAN 2023 Annual Meeting Movement Disorders: Trials Session, AbbVie presented data from a post hoc analysis of the Phase III M15-736 study (NCT04380142) investigating adverse events (AE) and discontinuation rates in 74 participants who received ABBV-951. Safety was assessed in the study participants who had dosing levels titrated during the four-week optimisation period, followed by a stable dose regimen during the eight-week maintenance period. When comparing the four-week optimisation and eight-week maintenance periods, a greater number of AEs (74.3% versus 67.9%) and treatment discontinuations due to AEs (16.2% versus 7.1%) were found in the optimisation period. In addition, a greater proportion of patients experienced movement-related AEs during optimization versus the maintenance period of the study, including dyskinesia (10.8% versus 0%), on and off phenomenon (6.8% versus 1.8%), and falls (13.5% versus 8.9%). Furthermore, individual infusion-site AEs followed a similar trend, favouring the maintenance period. This included erythema (20.3% versus 21.4%), pain (21.6% versus 8.9%), cellulitis (10.8% versus 12.5%), bruising (6.8% versus 1.8%), and nodules (5.4% versus 3.6%). Investigators suggested that the higher rates of AEs and discontinuations during optimisation may have been the result of the dose titration process and acclimation to a new drug delivery system.
At the AAN 2023 Contemporary Clinical Issues Plenary Session, NeuroDerm presented data evaluating the three-year outcomes in an open-label extension study in patients with advanced PD who received ND0612 treatment (NCT02726386). In Year 1 of the study, 60.5% of patients had an infusion-site reaction including nodules (50.0%), bruises or hematoma (36.8%), infection (36.8%), eschar (27.2%), erythema (10.5%), and inflammation (7.0%). But infusion-site reaction rates greatly diminished in years two and three of the study. The investigators attributed this decrease to patients becoming more adept at cleaning the infusion sites. Overall, infusion-site reaction led to study discontinuation in 3.5% of patients over three years.
Pivotal trials have demonstrated an improved time with subcutaneous continuous levodopa infusions against oral levodopa therapy. However, a head-to-head comparing ABBV-951 and ND0612 does not appear to be on the horizon yet. KOLs noted that the administration of ND0612 required two injection entry points compared to AbbVie’s one. It is unknown whether the additional injection entry point with ND0612 sites could lead to a higher rate of infusion-site reactions. Overall, KOLs were enthusiastic about the ability to control motor fluctuations and improve patients’ quality of life without the need for invasive surgery such as deep brain stimulation or the installation of Duodopa. However, they emphasized that success of these levodopa infusion systems requires education programs for patients and caregivers to maintain these devices, avoid infusion-site reactions, and reduce rates of discontinuation.