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AED IX - Highlights of Day Three: Updates on Drugs in the Pipeline
The Ninth Annual Antiepileptic Drug Trials Conference sponsored by the University of Pennsylvania Medical Center and the Epilepsy Therapy Development Project, explored:
Updates on antiepileptic drugs in the pipeline were reported at a unique gathering of world-renown physicians and corporate leaders on a day called Drugs in the Pipeline and the CNS/ Epilepsy Company Forum at the Ninth Annual Antiepileptic Drug Trials Conference. The meetings brought together representatives from academia, the business community, and regulatory agencies who share a common interest – bringing new therapies to market that will prevent seizures and improve the quality of life for patients with epilepsy.
According to Warren Lammert, Chairman and Co-Founder of the Epilepsy Therapy Development Project (Epilepsy TDP), which has been awarding grants to scientists to develop promising new therapies, “A key aspect of the presentations included both new drug updates and also innovative devices that could be a significant help for those with refractory epilepsy. At least 30 percent of approximately 50 million people world-wide have seizures that are still uncontrolled by available medications.”
Jacqueline French, MD, symposium director, said, “This gathering of stakeholders reflects our mission of bringing new treatments to patients.” Dr. French is Professor of Neurology at the University of Pennsylvania School of Medicine and also co-director of the Epilepsy Study Consortium with Orrin Devinsky, MD, Professor of Neurology, Neurosurgery, and Psychiatry, New York University and Director of their Comprehensive Epilepsy Center. Dr. French noted that “The consortium itself is working to facilitate good research by nurturing novel ideas for early proof-of-principle trials and helping with recruitment of study subjects.”
Promising Therapy Updates
There were presentations on brivaracetam, carisbamate, eslicarbazepine, fluorofelbamate, ganaxalone, huperzine A, JZ-P, lacosamide, retigabine, rufinamide, seletracetam, valproate derivatives, vigabatrin, clobazam, non-sedating barbiturates and novel AEDs that interact with SV2A ligands.
Ganaxolone is being developed to treat infantile spasms, as well as other epilepsy syndromes, by Marinus Pharmaceuticals. Earl Giller, MD, PhD, vice president for clinical development at Marinus Pharmaceuticals, said “Ganaxolone is a neurosteroid, which would be the first in its class to come to the market. If the clinical studies are successful, it will probably become available in 2010. Our goal is a compound that helps patients with infantile spasms and other forms of epilepsy. Because infantile spasms are so rare, and different experts have had different experiences with these patients, conducting drug studies is a challenge. Yet there are very few medications that are effective for infantile spasms. We hope that ganaxolone will not only be effective, but will have fewer adverse effects than other currently available effective treatments. Marinus has begun clinical trials for both infantile spasms as well as an adult add-on study in refractory partial onset seizures.”
Dr. Giller also talked about the value of feedback from epileptologists. “A conference such as this one is very important. The presentations and discussions help to develop subsequent protocols and perhaps to incorporate novel assessments that we may not have done otherwise,” he said.
Support from Epilepsy TDP
The Epilepsy TDP and the Epilepsy Research Foundation (ERF) provided seed money to Marinus Pharmaceuticals for ganaxalone development. The Epilepsy TDP and the ERF provided support to Harvard Medical School and Steven Schachter, MD, for a clinical trial of huperzine A, to EPINANO for Magnetonanoparticles, to Prof. Meir Bialer and Hebrew University of Jerusalem for valproate derivatives, and to NeuroAdjuvants for galanine. NeuroGenomics received a grant from ERF as well as a direct investment from ETDP and, and VistaGen Therapeutics was given a bridge loan by ETDP.
Tom Sutula, MD, PhD, Chair of the Department of Neurology, University of Wisconsin, and Chief Technical Officer, NeuroGenomeX, Inc, has received support from Epilepsy TDP and ERF to advance the development of 2-deoxy-D-glucose (2DG), a glucose analog used for decades as an image tracer, but which has possible use as a novel anticonvulsant and disease-modifying treatment for epilepsy.
Steven C. Schachter, MD, Professor of Neurology, Harvard Medical School, spoke about huperzine A, a compound found in Chinese club moss that is traditionally used for fever, swelling, and inflammation and that shows promising activity in animal models of epilepsy and pain. He said: “Huperzine A is widely used in China for Alzheimer’s disease, and has been studied in patients with benign senescent forgetfulness, vascular dementia, and myasthenia gravis. While there is no published experience in epilepsy, huperzine A has been studied in 1,400 volunteers and patients and appears to be safe and effective.”
The prospects for gene therapy were presented by Christine Sapan, PhD, from Neurologix, who said, “Gene therapy is a 21st century solution to neurogenic disease.” Their team has been looking at seizure reduction in animal models targeting temporal lobe epilepsy and trials are expected to begin this year. This would be offered as an alternative treatment for patients who have had no success with medications and are not candidates for epilepsy surgery.
A full list of presenters can be found at the Epilepsy Therapy Development Project website at www.epilepsyTDP.org.
Overcoming Barriers to Success
The afternoon sessions focused on Partnership and Financing Opportunities in Epilepsy, CNS: Corporate and VC Perspectives, moderated by Garry Menzel, PhD, and The Role of the CRO in the Clinical Development of Epilepsy/ CNS Drugs, which was moderated by Stephen Collins, PhD, Ovation Pharmaceuticals, Deerfield, Ill., and Warren Lammert.
Difficulties encountered in recruiting and enrolling patients in clinical trials were echoed throughout the morning session and possible solutions were discussed during the afternoon session. Dr. French acknowledged that enrollment in trials is a challenge, and added that one of the roles of the Epilepsy Study Consortium is to provide “one-stop shopping” that facilitates subject recruitment and enrollment.
The difficulty with recruitment was underscored by CRO presenter Michael Cioffi, executive director of INC Research, Raleigh, North Carolina. “A trial will not succeed if it doesn’t have patients,” he said. Referring to a study for progressive myoclonic epilepsy, he said, “We had to go through 185 sites in order to find 34 sites that would be appropriate to conduct this clinical trial.”
Looking at the Pipeline
In reviewing the conference highlights, Warren Lammert said: “For parents, families, and people living with epilepsy, this is the most importance conference of the year -- it is all about new therapies and an opportunity to see where the new therapies are in their development – a kind of status report on the pipeline. We were pleased to see an exciting array of new therapies representing a broad variety of approaches at many stages of the development process.”
“We are especially encouraged that for people with severe epilepsy, such as Lennox-Gastaut syndrome, drugs used successfully in Europe will be making their way to the United States. There are a number of other drugs in Phase Two and Phase Three clinical trials which have the promise to be filed with regulatory authorities over the next two to three years,” he said.
Mr. Lammert added, “From a practical point of view, and no less important, we learned of several programs to develop new benzodiazepine rescue medications for use by caregivers for stopping seizure clusters in first aid applications, such as more convenient intranasal dose formulations.”
Finally, he commented on two new devices that were presented at the meeting under development by Medtronic and NeuroPace. “With both of these devices,” he said, “we could see regulatory submission in the next 18 months.”
Edited by Steven C. Schachter, MD
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