NeuroDerm Announces Presentation of Data from Studies Evaluating ND0612, an Investigational Levodopa Continuous Administration Drug, in Healthy Volunteers and in Patients with Advanced Parkinson's Disease

NESS ZIONA, Israel, June 19, 2013 /PRNewswire/ --

NeuroDerm, Ltd. today announced that results from a phase I study in volunteers, and preliminary results from a phase IIA study in advanced Parkinson's patients, of ND0612, were presented at the 2013 International Congress of Parkinson's Disease and Movement Disorders. ND0612 is a proprietary levodopa/carbidopa liquid drug formula under development for continuous administration through a sub-cutaneous (SC) delivery patch that would maintain constant levodopa plasma concentrations.

ND0612 has been shown in both trials to be safe and tolerable and, for the first time in man, to maintain steady state, clinically meaningful levodopa plasma concentrations.  ND0612 can be administered subcutaneously in a convenient manner and has the potential to significantly improve the current standard of treatment of Parkinson's disease patients.

"We are encouraged by ND0612's potential to achieve steady state levodopa plasma levels both day and night and by its potential to become a widely accessible drug. Based on the positive data, as well as on discussions with the Food and Drug Administration, NeuroDerm is planning to continue the clinical development of ND0612 and initiate advanced clinical trials with ND0612 in the coming months",  said Oded S. Lieberman, PhD, NeuroDerm's CEO.

Data Presentations

Constant Therapeutic Levodopa Plasma Concentrations Maintained by Continuous Subcutaneous Administration of ND−0612, a Novel Formulation of Levodopa/Carbidopa

(Abstract #452)

Y. Caraco^[1], S. Oren^[3], P. LeWitt^[2]

^[1]HCRC, Hadassah Medical Center, Jerusalem, Israel; ^[2]Neurology, Wayne State University and Henry Ford Hospital, West Bloomfield, Michigan, USA; ^[3]NeuroDerm, Ltd, Ness Ziona, Israel

Data from 54 volunteers showed that continuous SC delivery of ND0612 is safe, tolerable  and achieved dose dependent, constant, LD plasma concentrations. ND0612 decreased LD plasma fluctuations and its peak-to-trough ratio and could be administered at differing day and night infusion rates. ND0612 could also be administered together with other oral PD medications such as entacapone.

Additional key findings presented include:

• Fifty-four healthy male Caucasians volunteers, aged 18 - 40 years, were tested in a Phase I, dose-escalating, randomized double-blind placebo-controlled study of ND0612.
• ND0612 was administered continuously via a SC infusion pump over 24 hrs. The dose of ND0612 was escalated based on the review and approval of a Data Monitoring Committee. LD/CD doses ranged between 120/30 and 360/90 mg LD/CD per 24 hrs.
• All subjects completed the study and its follow up. There were no significant systemic adverse events related to SC administration of ND0612. No clinically relevant effects were encountered in laboratory measurements or vital signs.
• Good local tolerance was observed, as demonstrated by mean Draize scores <1, lack of pruritus and skin staining, and only one reported adverse event of pain. In some subjects, small and tender nodules (~0.5cm in diameter) were detected upon deep palpation; these disappeared within several days or weeks.
• Constant LD and CD concentrations were maintained during the 9 hours of PK sampling. LD, CD and 3-OMD plasma concentrations increased linearly as a function of dose (infusion rate) of ND0612.
• Administration of ND0612 at a low night rate (80μl/h) and a high day rate (240 μl/h) resulted in respective lower and higher plasma concentration of LD. The time to reach steady state concentrations after changing the rate of administration was approximately 4 hours. An increase in the rate of administration several hours prior to waking would possibly prevent morning akinesia.
• Administration of ND0612 together with repeated dosing of oral entacapone 200 mg showed an increase in LD plasma concentrationof ~50%, with corresponding decrease in 3-OMD plasma concentration.

ND0612, A Novel Formulation Of Levodopa/Carbidopa For Continuous, Subcutaneous Administration, Achieves Steady-State Levodopa Plasma Concentrations In Parkinson's Disease Patients

(Abstract #LBA26)

Y. Caraco^[1], S. Oren^[2], O. Yacoby-Zeevi^[2], P. LeWitt^[3], N. Giladi^[4]

^[1]Clinical Pharmacology Unit, Hadassah University Hospital, Jerusalem, Israel; ^[2]NeuroDerm, Ltd, Ness Ziona, Israel;^[3]Neurology, Wayne State University and Henry Ford Hospital, West Bloomfield, Michigan, USA; ^[4]Neurology, Tel Aviv Medical Center and Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel

Preliminary data from 8 advanced Parkinson's disease patients showed that subcutaneous ND0612 delivery achieved steady-state plasma LD concentrations ranging from 700-900 ng/ml (which is a typical therapeutic range). Fluctuations in LD plasma concentration were significantly reduced. With ND0612, LD concentration could be adjusted by controlling the infusion rate (programmed during day and night) and by adding oral LD/CD and a COMT inhibitor. Peripheral catechol-O-methyl transferase (COMT) was probably the main metabolic pathway acting on LD. The amount of entacapone provided in Stalevo® was apparently insufficient to inhibit the extensive COMT activity. Therefore, we conclude that, with ND0612, additional inhibition of COMT would further contribute to increasing plasma LD concentration.

Additional preliminary key findings presented include:

• Study design: Randomized, double-blind crossover trial
• Subjects: 8 PD patients with motor fluctuations
• Treatment arms: ND0612 (LD/CD 6%/1.5%) or placebo, administered over 24 hrs together with two Stalevo® 100 doses, at bedtime (22:00) and again in the morning (09:00)
• Dose: During the day, ND0612 was administered at 240 μl/hr over 16 hrs and at night, 80 μl/hr over 8 hrs, for a total of 4.5ml/24hr (total LD/CD intake: 270/67 mg)
• Overall, the subcutaneous administration of ND0612 was associated with a favorable safety profile, similar to the healthy volunteers
• ND0612, delivered subcutaneously, achieved steady-state plasma LD concentrations ranging from 700-900 ng/ml (typical therapeutic concentrations of LD)
• The LD plasma concentration in patients in this study was 50-100% higher than encountered in our previous study of young healthy volunteers
• ND0612 significantly reduced (10- to 20-fold) the fluctuations of LD plasma concentration and markedly increased the time LD plasma concentrations were above 900-1200 ng/ml (considered to be therapeutic)

About Parkinson's Disease

Parkinson's disease affects approximately 6M patients in the world. It is caused by decreasing dopamine signaling in the brain as dopaminergic brain cells die off. Levodopa is the "Gold Standard" therapy for Parkinson's disease and virtually all patients receive it. When administered through the oral route, however, levodopa combined with a decarboxylase inhibitor (carbidopa or benserazide) demonstrates a short clearance half-life and low bioavailability that contribute to motor complications in Parkinson's disease patients. Stable levodopa blood levels have been the main challenge of Parkinson's drug therapy, and ways to achieve this have been under investigation for several decades.

About ND0612

ND0612 is based on a proprietary sub-cutaneous levodopa/carbidopa drug formulation that bypasses the digestive tract. It continuously delivers levodopa to achieve straight-line and clinically-significant levodopa blood levels.  It also delivers subcutaneous carbidopa to improve the bioavailability of levodopa. ND0612 is being developed for administration via a subcutaneous delivery patch as a new treatment and intervention option in Parkinson's disease treatment. It should significantly improve the management of motor fluctuations even in patients under the best current standard of care with oral levodopa therapy.

About NeuroDerm

NeuroDerm is an emerging pharmaceutical company that develops therapies for the treatment of CNS diseases. NeuroDerm's technology is based on proprietary reformulations of well-established oral drugs that achieve better efficacy. The company's lead products are ND0611 and ND0612, novel sub-cutaneous drug formulations for the treatment of Parkinson's disease, and ND0801, a combination drug for the treatment of cognitive disorders in diseases such as ADD/ADHD, schizophrenia and Alzheimer's disease. NeuroDerm is headquartered in the Weizmann Science Park, Ness Ziona, Israel.

Contact:
Oded S. Lieberman, PhD MBA, Chairman & CEO
[email protected]
Tel.: +972-8-946 2729; Cell: +1-617-517 6077

SOURCE NeuroDerm Ltd