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ND0612 beat oral levodopa/carbidopa at curbing motor symptoms

Aug 30, 2023Aug 30, 2023

A Phase 3 trial is testing the under-the-skin formulation of levodopa/carbidopa

by Marisa Wexler, MS | August 31, 2023

ND0612, a formulation of levodopa/carbidopa delivered continuously under the skin by a pump, was more effective than standard oral levodopa/carbidopa at controlling motor symptoms of Parkinson’s disease without causing problematic side effects.

Those top-line findings from the Phase 3 BouNDless clinical trial were announced earlier this year, and more detailed results were presented recently at the International Congress of Parkinson’s Disease and Movement Disorder Society (MDS) in Copenhagen, Denmark.

The presentation was led by Mitsubishi Tanabe Pharma America (MTPA), the company that plans to sell ND0612 in the U.S. if it is approved. MTPA is owned by Mitsubishi Tanabe Pharma Corporation, which is developing ND0612 through its subsidiary NeuroDerm.

“We are thrilled to present these positive results from our ongoing Phase 3 BouNDless trial, as they help us further understand the effect of ND0612 in people with Parkinson’s disease experiencing motor fluctuations,” Yasutoshi Kawakami, president of MTPA, said in a press release.

“The outcome of this trial exemplifies our commitment to continue recognizing the unmet needs of people living with this disease, and we look forward to sharing additional study findings with the scientific community,” Kawakami added.

Parkinson’s disease is caused by the dysfunction of cells in the brain responsible for making a signaling molecule called dopamine; reduced dopamine signaling ultimately leads to most symptoms of Parkinson’s. Levodopa plus carbidopa is a standard treatment for Parkinson’s that basically works by giving the brain more raw materials with which to make dopamine. Specifically, levodopa can be converted into dopamine by cells in the brain, and carbidopa helps levodopa get into the brain so it can be effective.

While levodopa and carbidopa can help to ease Parkinson’s symptoms, over the long run this treatment tends to lose efficacy, so many patients experience “off” time when symptoms aren’t controlled between doses. Long-term treatment with these medications also commonly causes dyskinesia (uncontrolled movements) as a side effect.

Standard levodopa and carbidopa therapy is taken orally. ND0612 contains the same therapies delivered continuously under the skin using a pump, similar to ones that sometimes are used to deliver insulin for people with diabetes.

The BouNDless (NCT04006210) trial enrolled 381 people with Parkinson’s whose symptoms were incompletely controlled with standard oral levodopa and carbidopa. After initial screening periods to determine the optimum dose for each patient, participants in the trial were assigned randomly to receive treatment with standard oral levodopa/carbidopa, or with ND0612, for about three months.

Results showed that the average daily “on” time, when symptoms were well-controlled without dyskinesia, was nearly two hours longer with ND0612 than with oral therapy. Congruently, daily “off” time when symptoms were not controlled, was significantly shorter with ND0612 compared with oral levodopa/carbidopa.

ND0612 also outperformed the oral therapy on the Patient Global Impression of Change (PGIC) and the Clinical Global Impression of Improvement (CGI-I), which are measures of overall health status rated by patients and their clinicians, respectively.

Scores on part two of the MDS-Unified Parkinson’s Disease Rating Scale Part (UPDRS), which assesses the extent to which Parkinson’s motor symptoms cause problems in day-to-day life, also showed significant improvement with ND0612 compared to oral therapy.

Safety data from the trial suggested that the overall safety profile is similar with ND0612 compared to oral levodopa and carbidopa, though patients on ND0612 were more likely to experience reactions at the infusion site, such as pain, redness, infection, and bruising. Rates of discontinuation from the trial were low for patients on either form of treatment.

Based on positive data from the trial, NeuroDerm previously announced plans to seek approval of ND0612 in the U.S. and Europe.