Innovation in drug formulations and delivery systems is one of the most rapidly changing areas in Parkinson’s disease (PD) treatment and is primarily driven by the levodopa market. At the American Academy of Neurology (AAN) 2024 Annual Meeting, data on NeuroDerm’s ND0612 (levodopa/carbidopa, LD/CD) and AbbVie’s Produodopa/Vyalev (foslevodopa/foscarbidopa) were showcased for the treatment of PD in anticipation of their US approvals later this year, says GlobalData, a leading data and analytics company.

Erela Dana, Director of Neurology at GlobalData, comments: “The new delivery systems by AbbVie and NeuroDerm offer a 24-hour continuous subcutaneous (SC) infusion of levodopa and are proposed to improve the rate of compliance while reducing risk of motor fluctuations and levodopa-induced complications such as levodopa-induced dyskinesia and “off” episodes.”

According to GlobalData’s Drug Database, there are three subcutaneous infusion devices in late stage (Phase III – Pre-registration) pipeline in the US. While Produodopa/Vyalev and ND0612 offer continuous levodopa infusion, Supernus’s SPN-830 is a SC apomorphine infusion device. When comparing the SC continuous infusion of levodopa and apomorphine, key opinion leaders (KOLs) previously interviewed by GlobalData stated a preference for levodopa formulations as it is the naturally occurring precursor to dopamine, which is converted in the brain.

Efficacy data and subgroup analysis presented by NeuroDerm from a randomized controlled Phase III study (BouNDless; NCT04006210) at AAN 2024 showed that treatment with an optimized ND0612 regimen provided an additional 1.72 hours of “on” time without troublesome dyskinesia compared with immediate-release LD/CD. The subgroup analysis demonstrated a homogeneous treatment effect in relation to “on” time improvements and minimal differences in safety and tolerability.

Dana comments: “The lack of differences seen in therapeutic effect and safety and tolerability of ND0612 across the different analyzed subgroups, including age, sex, body mass index (BMI), and geographical region, suggests wide adoption potential for the drug in all advanced PD patients with severe motor fluctuations.”

AbbVie presented the long-term safety and tolerability of Produodopa/Vyalev (NCT04379050) from an open-label extension (OLE) study of advanced PD patients. Overall, 83.7% of patients experienced ≥1 adverse events (AEs), with infusion site erythema and cellulitis being two of the most common AEs experienced by 16.3% and 15.5% of patients, respectively.

Dana adds: “The success of levodopa infusion systems requires avoidance of infusion-site reactions and reduced discontinuation rates due to safety and tolerability issues. The OLE outcomes presented by AbbVie address some of these concerns through the demonstration of a long-term favorable safety profile.”

Produodopa/Vyalev was launched in Germany, Spain, the UK, and Japan in 2023, and in France, Italy, and Canada in early 2024; However, its US launch hit a snag when it received a complete response letter (CRL) in March 2023.

Dana concludes: “NeuroDerm’s ND0612 is anticipated to launch in the US market later this year with an FDA Prescription Drug User Fee Act (PDUFA) date of Q2 2024, meaning that it could beat AbbVie in the race to US commercialization. However, if both products receive US approval, real-world evidence (RWE) and longer-term follow-up data could provide a competitive edge in the absence of a head-to-head trial comparing Produodopa/Vyalev and ND0612.”