NeuroDerm Announces Publication of Positive Results from Phase 3 BouNDless Trial Evaluating ND0612 in Parkinson's Disease Patients with Motor Fluctuations

• Data published in The Lancet Neurology showed favorable efficacy of ND0612 compared to oral immediate-release levodopa/carbidopa

REHOVOT, Israel, March 18, 2024 /PRNewswire/ -- NeuroDerm Ltd., a wholly owned subsidiary of Mitsubishi Tanabe Pharma Corporation (MTPC), today announced the publication of results in The Lancet Neurology from the pivotal, Phase 3 BouNDless trial (NCT04006210).

Results from the trial, which evaluated the efficacy, safety and tolerability of investigational ND0612 ? a continuous, 24 hours/day subcutaneous (SC) infusion of liquid levodopa/carbidopa (LD/CD) ? in comparison to oral immediate-release (IR) LD/CD in Parkinson's disease (PD) patients with motor fluctuations, met its primary endpoint and the first four secondary endpoints, and showed ND0612 was superior at increasing "ON" time without troublesome dyskinesia and reducing "OFF" time, compared to oral IR-LD/CD after 12 weeks.

"Orally administered levodopa/carbidopa tablets remain the most essential pharmacological intervention in Parkinson's disease; however, over time, the reliability of its benefits can decrease, leading to the onset of motor fluctuations", said Professor Alberto Espay, Principal U.S. Investigator of the BouNDless trial and Director of the James J. and Joan A. Gardner Family Center for Parkinson's Disease and Movement Disorders at the University of Cincinnati. "We are encouraged by these positive data, which we believe support ND0612, if approved, as a potential treatment option for people with Parkinson's disease experiencing motor fluctuations who have thus far had limited options."

Study participants entered an open label IR-LD/CD optimization phase followed by an open label ND0612 plus IR-LD/CD optimization phase and were then randomized to a 12-week double-blind double-dummy (DBDD) treatment period with either ND0612 or oral IR-LD/CD regimens. Key study findings include:

• Treatment with ND0612 demonstrated superior efficacy with a statistically significant addition (p<0.0001) of 1.72 hours in "ON" time without troublesome dyskinesia over oral IR-LD/CD, thus meeting the trial's primary endpoint.
• The trial also demonstrated statistically significant and clinically meaningful results for the first four secondary endpoints, including the key secondary endpoint with an additional 1.4-hour reduction in daily "OFF" time (p<0.0001) with ND0612 vs. oral IR-LD/CD.
• Additional secondary endpoints that reached statistical significance and clinically relevant improvement for both patients and their physicians were the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II scores (-3.05 [-4.28, -1.81], p<0.0001), the Patients Global Impression of Change (Odds Ratio [OR]: 5.31 [2.67, 10.58], p<0.0001) and Clinician Global Impression of Improvement (OR: 7.23 [3.57, 14.64], p<0.0001).
• The systemic safety profile of ND0612 was consistent with the well-established safety profile of oral standard of care LD/CD. As expected, due to its mode of continuous subcutaneous administration, infusion site reactions (ISRs) were the most frequent reported treatment emergent adverse events (57% for ND0612 vs. 43% for IR-LD/CD during the DBDD period of the study). Most ISRs were of mild severity. Of note, dyskinesia, falls and ON/OFF phenomena were reported less frequently in the ND0612 group compared to the IR-LD/CD group.
• Additionally, only 6% of study participants in the ND0612 group discontinued the trial during the DBDD period due to any reason, compared to 6% in the oral IR-LD/CD group. 

"Motor fluctuations are an all-too-common symptom associated with the use of oral LD/CD in Parkinson's disease, often causing significant disruptions to day-to-day life as the disease progresses," said Tami Yardeni, EVP, Clinical Development, NeuroDerm. "We now have compelling evidence to support the favorable benefit-risk profile of ND0612. These results show significant improvement of motor fluctuations, as well as improvements in the experiences of daily living for this challenging patient population."

Analyses of results from the ongoing BouNDless trial complement the long-term safety data from the BeyoND study (NCT02726386) including patients in their eighth year of follow-up.¹ 

About Parkinson's Disease 
Parkinson's disease affects more than 10 million people worldwide. It is caused by decreasing dopamine signaling in the brain as dopaminergic brain cells die off.?Levodopa is the most important replacement therapy for Parkinson's disease, administered together with a levodopa degradation inhibitor (usually carbidopa).?Oral levodopa intake leads to fluctuating plasma concentrations, with high peaks and low troughs that contribute to the progressive emergence of disabling clinical oscillations over the day in the motor function of many people with Parkinson's disease.?With disease progression, adjustments in oral levodopa therapy become less and less effective in managing such motor complications, leaving patients with limited treatment options that are highly invasive. 

About ND0612
ND0612 is an investigational drug-device combination therapy ? a 24-hours/day, continuous subcutaneous (SC) infusion of liquid levodopa/carbidopa (LD/CD) for the treatment of motor fluctuations in people with Parkinson's disease (PD). The safety and efficacy of ND0612 in PD is under review by the U.S. Food and Drug Administration (FDA) who has assigned a Prescription Drug User Fee Act (PDUFA) target action date for the second quarter of CY (calendar year) 2024.

About NeuroDerm, Ltd. 
NeuroDerm, Ltd. is a wholly owned subsidiary of Mitsubishi Tanabe Pharma Corporation (MTPC), based in?Israel, inspired to reduce disease burden and improve the quality of life?of patients and their families through innovative?drug-device combination therapies and technologies. NeuroDerm is a pharmaceutical and medical technology integrated company developing central nervous system (CNS) product candidates that are designed to address major deficiencies of current treatments. For additional information, please visit NeuroDerm's website at?www.neuroderm.com or follow us on LinkedIn. 

About Mitsubishi Tanabe Pharma Corporation 
Mitsubishi Tanabe Pharma Corporation (MTPC), the pharma arm of Mitsubishi Chemical Group (MCG), is one of the oldest pharmaceutical companies in the world, founded in 1678, and focusing on ethical pharmaceuticals. MTPC is headquartered in Doshomachi, Osaka, the birthplace of Japan's pharmaceutical industry. MCG has positioned health care as its strategic focus in its management policy, "Forging the future". MTPC sets the MISSION of "Creating hope for all facing illness". To that end, MTPC is working on the disease areas of central nervous system, immuno-inflammation, diabetes and kidney, and cancer. MTPC is focusing on "precision medicine" to provide drugs with high treatment satisfaction by identifying patient populations with high potential for efficacy and safety. In addition, MTPC is working to develop "around the pill solutions" to address specific patient concerns based on therapeutic medicine, including prevention of diseases, pre-symptomatic disease care, prevention of aggravation and prognosis. For more information, go to https://www.mt-pharma.co.jp/e/.

About Mitsubishi Tanabe Pharma America, Inc. 
Based in Jersey City, N.J., Mitsubishi Tanabe Pharma America, Inc. (MTPA) is a wholly owned subsidiary of Mitsubishi Tanabe Pharma Corporation's (MTPC) 100% owned U.S. holding company, Mitsubishi Tanabe Pharma Holdings America, Inc. It was established by MTPC to commercialize approved pharmaceutical products in North America. For more information, please visit www.mt-pharma-america.com or follow us on Twitter, Facebook and LinkedIn.

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¹S Isaacson, et al. Long-term safety of continuous levodopa/carbidopa infusion with ND0612: Results from the ongoing BeyoND study. Poster presented at: American Academy of Neurology Annual Meeting; 2022 Apr 2-7; Seattle, WA.

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