ND0612 Better Than Oral Levodopa at Prolonging ‘On’ Time: Phase 3 Trial
Approval requests expected for levodopa/carbidopa given via 24-hour pump
A liquid formulation of levodopa/carbidopa (LD/CD) delivered continuously under the skin via a pump, ND0612 is more effective than oral LD/CD, a mainstay treatment, at controlling symptoms without causing dyskinesia, according to results from the Phase 3 BouNDless trial.
With this finding, the trial met its primary goal — that of providing levodopa/carbidopa benefits while diminishing troublesome dyskinesia, the involuntary movements associated with long-term levodopa use.
NeuroDerm, which is developing ND0612, now plans to apply to the U.S. Food and Drug Administration (FDA) this year asking for ND0612 to be approved. The company also expects to request its approval in Europe.
“We are extremely encouraged by the positive outcome of the Phase III BouNDless trial,” Tami Yardeni, executive vice president of clinical development at NeuroDerm, a Mitsubishi Tanabe Pharma Corporation subsidiary, said in a company press release.
ND0612 as potential alternative therapy to control motor fluctuations
“People with Parkinson’s disease experiencing motor fluctuations have limited options to manage their condition,” Yardeni said. “These remarkable results confirm the potential of ND0612 as an effective and well-tolerated treatment option to better control motor fluctuations — addressing a significant, unmet need.”
Full trial results and other data will be presented at upcoming medical conferences, NeuroDerm stated.
Parkinson’s is caused by the death of cells in the brain that make the chemical messenger dopamine and subsequent dopamine deficiency. Levodopa/carbidopa is a standard Parkinson’s treatment that works by providing the raw materials for making dopamine.
While currently available LD/CD treatments are taken orally, ND0612 delivers the same substances subcutaneously over 24 hours via a specialized pump, considered to be comparable to pumps commonly used to administer insulin for people with diabetes.
ND0612 is designed to improve LD/CD’s pharmacokinetics (movement into, through, and out of the body) by avoiding gastric involvement and maintaining stable and continuous therapeutic exposures.
Results from an open-label Phase 2 BeyoND clinical trial (NCT02726386) showed the therapy was generally well-tolerated over more than four years of treatment.
NeuroDerm then sponsored a Phase 3 trial of its pump therapy, called BouNDless (NCT04006210), to compare ND0612’s safety and effectiveness against oral LD/CD in Parkinson’s patients experiencing “off” episodes between standard treatment doses. Off periods refer to times when motor symptoms are no longer effectively controlled by the medication and re-emerge, but another dose cannot yet be taken.
The study enrolled 381 patients. After an initial screening and an adjustment period to determine their optimal dose of each therapy, participants were randomly assigned to either ND0612 or oral levodopa/carbidopa for 12 weeks (about three months). To keep the trial blinded, so that patients and researchers did not know who was on which treatment, placebo versions of each treatment also were given.
The trial’s main goal was to compare the amount of good “on” time, classified as the period of time when symptoms are well-controlled and patients are not experiencing troublesome dyskinesia as a levodopa side effect.
Lesser time with dyskinesia seen in patients using ND0612 in BouNDless trial
Over the three months of treatment, the average daily good on time was significantly higher, by 1.73 hours, with ND0612 compared with oral LD/CD, NeuroDerm reported.
ND0612 also outperformed oral levodopa/carbidopa at reducing “off” time — the study’s key secondary goal — and at easing the impact of motor symptoms on daily activities. Patient- and clinician-reported measures of improvement also favored the experimental therapy.
“With these positive results for the primary endpoint [goal] and four secondary endpoints, ND0612 has confirmed its potential as an effective treatment strategy for Parkinson’s disease patients with motor fluctuations, despite optimization of oral therapies,” said Alberto Espay, MD, the trial’s principal U.S. investigator.
The overall safety profile of ND0612 in the BouNDless study was generally comparable to the known profile of LD/CD therapy.
Infusion site reactions, such as redness, hematoma, and infection, were more common among patients on ND0612. By contrast, patients on oral LD/CD more frequently experienced falls and “on and off phenomena.”
Comparable proportions of people in both groups left the trial — 6.3% with ND0612 and 6.1% with oral LD/CD. Among those who did so due to side effects, the proportions were 5.5% with ND0612 and 3.1% with oral LD/CD.
“Continuous subcutaneous LD/CD treatment shows promise to change the treatment paradigm and transform the lives of patients with Parkinson’s disease,” added Espay, who is also the director of the James J. and Joan A. Gardner Family Center for Parkinson’s Disease and Movement Disorders at the University of Cincinnati.
Olivier Rascol, the trial’s principal investigator in Europe and Israel, and a professor at Toulouse University Hospital in France, considered its results to be “meaningful to both patients and healthcare providers, as there will be a novel, minimally invasive, continuous subcutaneous LD/CD treatment option demonstrating encouraging efficacy and tolerability.”
ND0612 is expected to help “patients stay on treatment with better motor function — an important milestone … for people with [Parkinson’s] experiencing motor fluctuations,” Rascol added.
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