, November 9, 2011
NeuroDerm, Ltd. announced today the results of a Phase I/II safety and pharmacokinetic trial of ND0611, administered as an adjunct therapy to Sinemet®, Sinemet® CR or Stalevo®, in patients with advanced Parkinson's disease. ND0611 is a proprietary carbidopa liquid formula administered sub-cutaneously via a dermal patch to increase the bioavailability and efficacy of orally- administered levodopa. Results of this study support the continued development of ND0611 for the treatment of Parkinson's disease.
This double-blind, randomized, six-way crossover study met all of its primary and secondary endpoints. The analysis showed that ND0611, when compared with placebo, showed meaningful, highly statistically significant improvement in all of the pharmacokinetic (PK) endpoints when administered with three most common oral levodopa therapies (immediate-release Sinemet®, Sinemet®-CR, and Stalevo®). The primary and secondary PK endpoints included levodopa half-life, the duration of levodopa concentration in excess of a threshold of 1000ng/ml in plasma, the area-under-the-concentration-time-curve and levodopa trough levels. The full results of this study will be presented at a future scientific meeting.
The most common adverse events across all treatment arms, including placebo, were vertigo, nausea, asthenia, back pain, myalgia, pain in extremity, headache and erythema. There were no clinically relevant effects seen in laboratory measured or vital signs.
"This first trial in patients of ND0611 hit all of its endpoints and was a complete success. ND0611 is an innovative treatment for PD and this important milestone justifies ND0611's further clinical and regulatory development," said Sheila Oren, MD, VP Clinical and Regulatory Affairs at NeuroDerm.
"One of our priorities at MJFF is to drive research that could improve the quality of life for people living with PD today," said Brian Fiske, PhD, director of research programs at MJFF. "NeuroDerm is working to develop a therapy that might do just that. By providing a more even and continuous supply of levodopa to the brain, ND0611 has the potential to limit the motor fluctuations that many patients experience during periods when their medication wears off."
"ND0611's remarkable success in its first phase I/II trial significantly raises the probability of it becoming a new treatment option for PD patients. ND0611 is unique: it is the first drug developed to administer carbidopa systemically; it acts directly on levodopa metabolism not only in the gastrointestinal tract; and it probably employs a different mode of action than orally administered carbidopa," said Oded S. Lieberman, PhD, NeuroDerm's Chairman and CEO. "ND0611 has now been shown to improve levodopa's bioavailability in patients with any type of oral levodopa drug used even improving the bioavailability of what is considered to be the best current levodopa oral therapy. One can now realistically hope that ND0611 may eventually establish a higher standard of care for PD patients undergoing oral LD therapy".
About the phase I/II Safety and Pharmacokinetic Study
This placebo controlled, randomized, double-blind, six-way crossover trial enrolled 24 patients with advanced Parkinson's disease. All patients were administered the three most commonly-used levodopa therapies (immediate-release Sinemet®, Sinemet®-CR, and Stalevo®) in 100mg dosage four times per day; in addition they received either ND0611 or placebo.
In addition to evaluating safety and tolerability, the study's primary endpoint was improvement in levodopa half life in all treatment arms; secondary endpoints included additional PK parameters. All PK parameters for each oral treatment mode were evaluated separately and showed statistical significance.
This trial was supported by a grant of $1 million by The Michael J. Fox Foundation for Parkinson's Research as part of the Foundation's Clinical Intervention Awards 2010 program.
About Parkinson's Disease
Parkinson's disease affects approximately 6 million 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. Levodopa is always co-administered with a degradation inhibitor (usually, carbidopa). When administered through the oral route, however, levodopa suffers from a short clearance half-life and low bioavailability that contributes to motor complications in Parkinson's patients.
ND0611 is based on a proprietary formulation that enables, for the first time, the continuous administration of carbidopa in a practical manner via a subcutaneous dermal patch. Carbidopa, conventionally co-administered with levodopa orally to prevent its breakdown, suffers from low bioavailability in itself. Continuous subcutaneous delivery of carbidopa should thus improve the bioavailability of oral levodopa, permit more continuous levels of levodopa to be maintained in the brain, improve the management of motor fluctuations in Parkinson's disease patients and result in a more efficacious usage of levodopa in Parkinson's disease therapy.
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 whose low bio-availability is the major impediment to better efficacy. The company's lead products are ND0611, a revolutionary skin patch for the treatment of Parkinson's disease and ND0801, a combination patch for the treatment of ADD/ADHD. Other programs focused at other diseases, including schizophrenia and Alzheimer's disease, are in different stages of development. NeuroDerm is headquartered in the Weizmann Science Park, Ness Ziona, Israel.
About The Michael J. Fox Foundation for Parkinson's Research
As the world's largest private funder of Parkinson's research, The Michael J. Fox Foundation is dedicated to accelerating a cure for Parkinson's disease and improved therapies for those living with the condition today. The Foundation pursues its goals through an aggressively funded, highly targeted research program coupled with active global engagement of scientists, Parkinson's patients, business leaders, clinical trial participants, donors and volunteers. In addition to funding more than $270 million in research to date, the Foundation has fundamentally altered the trajectory of progress toward a cure. Operating at the hub of worldwide Parkinson's research, the Foundation forges groundbreaking collaborations with industry leaders, academic scientists and government research funders; increases the flow of participants into Parkinson's disease clinical trials with its online tool, Fox Trial Finder; promotes Parkinson's awareness through high-profile advocacy, events and outreach; and coordinates the grassroots involvement of thousands of Team Fox members around the world. Now through December 31, 2012, all new and increased giving to The Michael J. Fox Foundation, as well as gifts from donors who have not given since 2009 or earlier, will be matched on a dollar-for-dollar basis with the $50-million Brin Wojcicki Challenge, launched by Sergey Brin and Anne Wojcicki.
For more information visit:
http://www.michaeljfox.org ; http://www.facebook.com/michaeljfoxfoundation.
Oded S. Lieberman, PhD MBA, Chairman & CEO
Tel.: +972-8-946-2729; Cell: +1-617-517-6077
SOURCE NeuroDerm Ltd