Mitsubishi Tanabe Pharma America (MTPA) presented new data from the Phase 3 BouNDless trial and its open-label extension (OLE) of ND0612 at the 2024 International Congress of Parkinson's Disease and Movement Disorders (MDS), highlighting the potential of ND0612 as a treatment for motor fluctuations in Parkinson's disease (PD). ND0612 is an investigational 24-hour, continuous, subcutaneous infusion of liquid levodopa/carbidopa (LD/CD).
The data showcased one-year outcomes from the BouNDless-OLE phase, consistent with previously reported 12-week data, reinforcing the long-term efficacy of ND0612. Additional findings from patient-reported outcomes favored ND0612 over oral immediate-release (IR) LD/CD in enhancing quality of life (QoL) and improving motor signs and motor experiences of daily living (m-EDL).
Sustained Reduction in OFF Time and Improvement in ON Time
Patients who completed the double-blind double-dummy (DBDD) phase of the BouNDless study were eligible to enter the OLE phase. At six months, patients treated with ND0612 experienced an average reduction of 2.2 hours in daily OFF time and an increase of 2.4 hours in daily ON time without troublesome dyskinesia. These results were sustained at 12 months, showing an average reduction of 2.02 hours in OFF time and an increase of 2.11 hours in ON time without troublesome dyskinesia.
Furthermore, patients with one or more hours of ON time with troublesome dyskinesia at ND0612 initiation (n=45) experienced an average reduction of troublesome dyskinesia by 1.5 hours at 12 months, demonstrating sustained efficacy in managing dyskinesia.
Enhanced Quality of Life
Following two sequential open-label periods to optimize oral IR-LD/CD and ND0612, study participants were randomized to a 12-week DBDD treatment period with either ND0612 or IR-LD/CD regimens. Change in QoL was assessed at the end of the DBDD period across eight domains of daily living using the PD Questionnaire-39 (PDQ-39).
At the end of 12 weeks, patients in the continuous 24-hour ND0612 treatment group reported improved QoL (-2.1 [-3.7, -0.6]) compared to no change in the IR-LD/CD group (+0.6 [-0.9, 2.1]). The PDQ-39 domain analyses favored ND0612 treatment in most domains, including mobility, bodily discomfort, cognition, activities of daily living, stigma, social support, communication, and emotional well-being.
Superior Improvements in Motor Signs and Daily Living Experiences
During the BouNDless trial, at both eight and 12 weeks, treatment with ND0612 showed superior improvements in m-EDL vs. oral IR-LD/CD, as measured by the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II and Part III scores.
Additionally, a post-hoc analysis of treatment differences for a number of motor signs showed treatment with ND0612 was superior to oral IR-LD/CD, with improvements observed in postural instability-gait disorder (–0.26 vs. 0.02, p =0.0012), speech and oral health (–0.11 vs. 0.05, p =0.0140), tremor (–0.15 vs. –0.05, p =0.0992), and self-care (–0.08 vs. 0.09, p =0.0528). No relevant differences were observed for rigidity and bradykinesia.
Safety and Tolerability
In the BouNDless trial, ND0612 was generally well tolerated. The most common systemic treatment emergent adverse events (TEAEs) reported during the open-label run-in period of the study included dyskinesia (9.3% of subjects), ON and OFF phenomenon and fall (each reported in 5.3% of subjects). During the maintenance period of the clinical trial, 2% of patients in both the ND0612 and oral IR-LD/CD-only groups reported dyskinesia. Additionally, only 6% of study participants treated with ND0612 discontinued the trial during the maintenance period due to any reason – including 5% due to AEs – compared to discontinuation rates of 6% and 3%, respectively, of study participants in the oral IR-LD/CD groups.
