Ryan Case, PhD, head of clinical medical affairs at NeuroDerm, spoke about the main findings from the phase 3 BouNDless trial of ND0612 for Parkinson disease.
Ryan Case, PhD
NeuroDerm recently announced ND0612, a 24-hour/day subcutaneous infusion of liquid levodopa/carbidopa (LD/CD), met its primary end point in the phase 3 randomized, double-dummy BouNDless trial (NCT04006210) with improvement in ON time for patients with Parkinson Disease (PD).1 The treatment is designed with the purpose of improving the pharmacokinetic profiles of oral LD/CD and maintaining therapeutic levodopa plasma concentrations.
Patients in the trial were randomly assigned, over the span of a 12-week treatment period, to ND0612 or placebo, and showed a significance difference of 1.72 hours in good ON time (P <.0001). The drug also demonstrated significant results with the key secondary end point of OFF time (P <.0001), along with the other end points including the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale Part II score (P <.0001), scales of impression of change.
Ryan Case, PhD, head of clinical medical affairs at Neuroderm, connected with NeurologyLive® to provide an overview of the results from the trial and expand on the data. He also noted some of the improvements that ND0612 could offer to the PD community as a therapy along with what patients with PD should take away from the findings.
Ryan Case, PhD: With current, limited options for people with Parkinson disease experiencing motor fluctuations, ND0612 has the potential—subject to regulatory approval—to change the treatment paradigm and become an effective, well-tolerated treatment option to better control motor fluctuations.
This is because, while levodopa is the standard of care therapy for Parkinson disease administered together with a levodopa degradation inhibitor (usually carbidopa), chronic oral levodopa therapy is often associated with the development of motor complications that result from fluctuating levodopa plasma concentrations (peaks and troughs), limiting its clinical utility. Continuous infusion is considered to be the optimal delivery route for treating patients with PD with motor fluctuations, but current infusion systems require invasive surgery.
As Parkinson disease progresses, the therapeutic window for levodopa concentrations shrinks, making it more difficult to maintain beneficial concentrations without going too low, which leads to OFF time, or too high, which leads to troublesome dyskinesia. As a continuous infusion, the concentration of levodopa is kept constant and allows more time within this therapeutic window.
Noteworthy findings from the BouNDless trial include that treatment with ND0612 demonstrated superiority over [immediate-release]-LD/CD with a statistically significant difference (P <.0001) of 1.72 hours in good ON time, defined as ON time without troublesome dyskinesia, from baseline to the end of the 12-week double-blind, double-dummy (DBDD) maintenance period. The trial also demonstrated positive and clinically meaningful results for the key secondary end point of OFF time (P <.0001) from baseline to the end of the 12-week DBDD maintenance period.
ND0612 also demonstrated superior efficacy on several predefined secondary end points, including the MDS-Unified Parkinson's Disease Rating Scale Part II score (the motor experiences of daily living sub-score), Patient Global Impression of Change, and Clinical Global Impression of Improvement.
ND0612 drug product is designed to improve the drugs’ pharmacokinetic profiles by avoiding gastric involvement and maintaining stable and continuous therapeutic levodopa plasma concentrations. It potentially offers reliable, sustained relief of motor fluctuations in people with Parkinson disease. ND0612 is currently the only continuous subcutaneous, levodopa/carbidopa product with such robust long-term safety data.
The long-term safety and tolerability profile of ND0612 is well documented with a cumulative exposure exceeding 550 patient-years and with some patients already in their 7th year of ND0612 treatment in the long-term safety trial. The tolerability profile of ND0612 looks very promising, with only 6.3% of patients randomized to ND0612 discontinuing the DBDD period of the pivotal efficacy study due to any reason, including 5.5% who discontinued due to adverse events.
Transcript edited for clarity.