A year-long treatment with ND0612, an investigational liquid formulation of levodopa and carbidopa delivered via continuous subcutaneous infusion, has demonstrated sustained reduction in motor symptom fluctuations and improved quality of life for individuals with advanced Parkinson's disease. The findings, presented at the 2024 International Congress of Parkinson's Disease and Movement Disorders (MDS), highlight the potential of ND0612 to provide a more consistent therapeutic effect compared to traditional oral medications.
The data comes from the BouNDless study (NCT04006210) and its ongoing open-label extension, BeyoND (NCT02726386), which compared ND0612 to immediate-release oral levodopa/carbidopa in patients with advanced Parkinson's. The trial was sponsored by Neuroderm, a subsidiary of Mitsubishi Tanabe Pharma Corporation (MTPC).
Sustained Motor Control and Improved Quality of Life
According to Gustavo A. Suarez Zambrano, MD, Vice President of Medical Affairs at MTP America, the longer-term data suggests that ND0612 not only improves symptoms but also maintains its efficacy, potentially offering patients a significant reduction in symptom burden.
In Parkinson's disease, the progressive loss of dopaminergic neurons leads to a deficiency in dopamine, resulting in motor and non-motor symptoms. Levodopa, combined with carbidopa, remains a primary treatment to alleviate motor symptoms by providing neurons with the building blocks to produce dopamine. However, long-term use can lead to dyskinesia and "off" episodes, where symptoms are not adequately controlled between doses. ND0612 aims to mitigate these issues by delivering a continuous supply of levodopa/carbidopa, minimizing fluctuations in drug levels.
Previous results from the BouNDless study, which assessed ND0612 over three months, showed an extension of daily "on" time (periods of controlled symptoms) and a reduction in "off" time compared to oral levodopa/carbidopa.
Impact on Motor Skills and Daily Living
The latest data presented at the MDS meeting further revealed that ND0612 improved motor signs and enhanced motor experiences in daily living, as measured by the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Patients on ND0612 showed improvements in areas such as speech, oral health, tremor, and self-care at both eight and 12 weeks. While rigidity and bradykinesia did not show significant differences between the treatment groups.
Furthermore, ND0612 led to improvements in patients' quality of life, as indicated by the Parkinson's Disease Questionnaire (PDQ)-39. Positive impacts were observed across multiple domains, including mobility, bodily discomfort, cognition, social support, stigma, communication, and emotional well-being.
The therapy was generally well-tolerated, with the most common side effects being infusion site reactions and side effects similar to those associated with oral levodopa/carbidopa, such as dyskinesia, motor fluctuations, and falls.
Long-Term Efficacy in Open-Label Extension
Data from the BeyoND open-label extension study showed that patients experienced an average reduction in off-time of 2.2 hours after six months and 2.02 hours after one year. Additionally, there was an increase in on-time without troublesome dyskinesia by 2.4 hours after six months and 2.11 hours after one year.
The U.S. Food and Drug Administration (FDA) is currently reviewing ND0612 for potential approval, which, according to Zambrano, could provide a new treatment option for Parkinson's disease patients experiencing motor fluctuations.
