AAN 2025: Stable motor control seen with long-term ND0612
Therapy better than standard treatment for Parkinson's patients in study
The investigational liquid therapy ND0612 — an around-the-clock supply of levodopa/carbidopa infused via a pump under the skin — provides more stable motor control in people with Parkinson’s disease who experience motor fluctuations than standard immediate-release levodopa/carbidopa.
That’s according to data from the randomized portion of the Phase 3 BouNDless (NCT04006210) study and its ongoing open-label extension. BouNDless tested the effectiveness, safety, and tolerability of ND0612 compared with immediate-release levodopa/carbidopa in more than 250 MS patients; in the extension, participants are receiving the therapy candidate for a period of up to 4.5 years.
These data were presented at the American Academy of Neurology (AAN) 2025 Annual Meeting, held April 5-9 in San Diego and online, by Rajesh Pahwa, MD, the director of the Parkinson’s Disease and Movement Disorder Center at the University of Kansas Medical Center.
“Continuous subcutaneous [under-the-skin] delivery of levodopa/carbidopa with ND0612 led to fewer daily transitions between motor states versus immediate-release levodopa/carbidopa” Pahwa said.
Pahwa’s oral presentation was titled “Impact of 24-hour Subcutaneous Levodopa/Carbidopa Infusion (ND0612) on Motor Function: Efficacy Outcomes from the Phase 3 BouNDless Study.” The study was funded by Neuroderm, the Mitsubishi Tanabe Pharma Group company that is developing ND0612. Pahwa has served as a paid consultant for Mitsubishi Tanabe and other pharmaceutical companies.
ND0612 delivers continuous infusion of levodopa/carbidopa
In Parkinson’s, the gradual loss of dopaminergic neurons — the nerve cells that produce the signaling chemical dopamine — leads to motor symptoms such as tremor and slowed movement. A combination of levodopa with carbidopa, which provides nerve cells with the building blocks to produce dopamine, is the mainstay treatment for easinge those symptoms.
However, long-term use of levodopa and carbidopa can lead to side effects, including uncontrolled movements known as dyskinesia. As the disease progresses, patients also often experience off time, periods when symptoms are not well controlled between scheduled doses.
Patients may experience motor fluctuations for various reasons, including a lack of response to treatment, wearing off toward the end of the dosing interval, and delayed on time, when levodopa/carbidopa takes longer than expected to start working.
ND0612 delivers a continuous infusion of levodopa/carbidopa under the skin. Unlike standard oral formulations, it maintains stable levels of levodopa/carbidopa in the blood. This is expected to help control motor fluctuations by preventing the lows in levodopa/carbidopa linked to off time.
Ideally, we would like a patient to be on all the time and not have to go from one motor state to the other.
The BouNDless study tested how well ND0612 works compared with immediate-release levodopa/carbidopa oral capsules in 259 people with Parkinson’s who were experiencing motor fluctuations. After an open-label run-in phase to establish the optimal dosing, participaents were randomly assigned to receive either ND0612 or immediate-release levodopa/carbidopa for 12 weeks, or about three months.
Patients were asked to keep home diaries detailing the number and duration of off times. They also were asked to record on time without dyskinesia, with nontroublesome dyskinesia, or with troublesome dyskinesia during the three days before each study visit.
“Ideally, we would like a patient to be on all the time and not have to go from one motor state to the other,” Pahwa said, referring to transitions from off to on motor states, or vice versa, during the course of a day.
Therapy continued to show safety, tolerability among MS patients
Previous data had shown that one year of treatment with ND0612 sustainably reduced the periods of off time and improved patients’ quality of life. Now, the research team shared data from post hoc analyses evaluating the effect of ND0612 on Parkinson’s motor states during the day in patients experiencing motor fluctuations.
At the end of the 12 weeks, patients on ND0612 experienced fewer off episodes than did those on immediate-release levodopa/carbidopa (2.4 vs 3.3 per day), as well as less off time (3.76 vs. 5.2 hours). These participants had an average of about two more hours each day of on time without any dyskinesia (9.37 vs. 7.43 hours), and also transitioned between motor states less often (5.3 vs. 7.1).
Patients who completed the randomized portion of the BouNDless study could enter the open-label extension. Of 232 patients, 167 (72%) received ND0612 for at least one year as part of the open-label extension. After this period, benefits continued, with 1.86 hours less of off time, 1.96 hours more of on time without troublesome dyskinesia, and 2.19 hours more without any dyskinesia, according to the data.
Consistent with earlier findings, ND0612 was shown to be “generally safe and well tolerated,” the researchers wrote in the presentation abstract. The most common side effects were reactions at the site of infusion.
Further, the researchers noted that “efficacy benefits were sustained at month 12.”
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