Epilepsy affects more than 50 million people worldwide and 3 million in the US alone, yet we rarely get a glimpse into the new medications, devices, and therapies under development that may help those in need. More than 30% of patients live with uncontrolled seizures, and countless more live on one or more medications while attempting to balance the side effects with the benefits.
The annual Epilepsy Pipeline Conference, hosted by the Epilepsy Therapy Project (ETP), provides a unique peak into what’s under development that patients may see in the coming years. Ten years ago there were only a handful of seizure medications to choose from. Now there are more than 15, with multiple new drugs under development. Just over a decade ago, the first hardware device, the Vagus Nerve Stimulator (VNS) entered the market and now other devices are under development or review by the FDA. Despite all of the research, the debate progresses on whether new epilepsy treatments currently get the industry attention they deserve when the annual number of new epilepsy cases equals that of breast cancer.
ETP’s President Joyce Cramer welcomed a large audience, including leading neurologists, companies, investors, press, and non-profits attending from around the country and the world. Henry Chesborough, PhD from UC Berkeley diagramed how the entire Life Sciences market is starting to mirror the technology market, with collaborative efforts and open, cooperative innovation gradually progressing to become the new industry standard for developing new medications and devices.
Robert Fisher MD, PhD from Stanford University and Epilepsy Center was uniquely positioned to provide a thorough overview of therapeutic devices under development, the fastest growing segment of epilepsy therapy and one that offers some of the most unique approaches. These devices, many surgically implanted, utilize a host of different seizure detection mechanisms and just as broad an array of possible outcomes ranging from treatment to prediction to simple seizure notification. Ivan Osorio, MD discussed the potential for this segment relative to medications and surgery. Frank Fischer from Neuropace led the review of devices on the market or in the pipeline. Cyberonics discussed the VNS, the only implantable device currently available to patients. Approved by the FDA in 1997 and now used by more than 50,000 epilepsy patients nationwide, the VNS is designed as an adjunctive therapy for patients experiencing limited success with medications. Other surgically implanted devices are under review by the FDA from Medtronic and NeuroPace, and all three companies provided insights on what interesting new features the next generation of implantable devices might offer. Earlier in development, NeuroVista presented a different approach to implantable devices, with their goal being the elusive but desirable outcome of an early warning system that could provide patients time to respond knowing that a seizure is likely. Intelli-Vision and BioLert presented completely external devices that serve simply as seizure notification tools to reduce the stress associated with the unpredictability of seizures. These wristwatches are not therapeutic, like the NeuroVista device, but simply informative, leveraging unusual motion detection and a combination of wireless, GPS and/or Bluetooth to notify parents and caregivers that their patient is currently experiencing a tonic clonic (grand mal) seizure.
A host of additional device solutions under development were presented, including brain cooling therapy, one that responds with drug therapy vs. electrical stimulation, one that combines magnetoparticles and MRI images, and a wireless helmet for portable EEG recording. This vast array in development seems to entrench devices as a permanent segment in epilepsy therapy.
New and Early Stage Anti-Seizure Medicines
Steven White, PhD and Stephen Collins, MD, PhD began the discussion on new anti-epileptic drugs (AED’s) under development by reviewing the structure and results of the development process. With 13 new medicines on the market since 1993 and several coming in the next 1-3 years, the sheer number of AED’s has more than doubled in less than 20 years. Despite all of the options, the percentage of patients with refractory seizures (not responding to medicine) has not significantly changed over time. While side effects have improved, one would think that all of these options would dramatically improve the success rates as well, but that has yet to happen. Collins and White then examined the pros and cons of the current drug development process in search of clues on why this would be.
NeuroVentures’ Dan O’Connell led review of 16 drugs and biologics now in the development pipeline in various stages of testing from companies including:
•Neurologix and Asklepios – Both use gene therapies for temporal lobe epilepsy
•Neuroadjuvants -- Focuses on the neuropeptide galanin for seizures and pain
•Medipro – Potential AED and neuroprotectant
•NeuroTherapeutics – Seizures and pain
•Catalyst – Next generation of AED Vigabatrin
•Medkura- Inhaled during aura to prevent pending or stop status epilepticus
•Paloma – Small molecule drugs for infantile spasms
Other companies with AED’s ready for testing or now being tested in people with epilepsy included BioLink, Marinus, Supernus, NeuroGenomeX, and SK Life Science.
Panel Discussions on Hot Topics
Subsequent panels discussed and debated hot topics aligned with the development of new AED’s and devices. Five bioscience venture capitalists confirmed their ongoing interest in new drugs, although they also admitted that the benchmarks for acceptance of relevant startups have risen in recent years. They debated the pros and cons of ‘virtual’ biotech firms and the timing for partnering with outside parties such as non-profits and large pharmaceutical companies. A private sector panel outlined solutions to common barriers, including FDA approvals, study designs, and the need to demonstrate a new drug’s novel mechanism of action to key parties. Neurologists discussed possible genes and biomarkers associated with sudden unexplained death in epilepsy (SUDEP), the causes for which remain mostly unknown. Finally, ETP’s President Joyce Cramer highlighted modes for leveraging non-profits like ETP and others. Partnership opportunities abound with ETP, including access to intelligence, grants and investments, and introductions to key industry influencers.
Late Stage Anti-Seizure Medications
James Cloyd, PhD explained approaches to novel formulations, while Jacqueline French, MD reviewed opportunities and issues for AED’s in late stage testing that are nearing final submission for FDA approval. Topics of discussion included the difficulty of recruiting qualified patients for clinical trials, the increasing cost of US studies and the trend towards international studies, and the resulting inconsistency of test results and the possible causes. Presentations described nine AED’s currently in the late stages of testing for the US market.
Eslicarbazepine – A sodium channel blocker related to carbamezipine (Tegretol) in phase 3 testing is applicable for partial onset seizures
Retigabine – A potassium channel opener for partial onset seizures currently under the final stages of FDA approval for release
Brivaracetam – Currently in phase 3 testing for adults with partial onset seizures
Carisbamate – Currently in phase 3 testing, unknown mechanism of action (since the conference, this drug development has been discontinued)
New Diazepam – The next generation of the auto-injector is in phase 3 testing
Parampanel – Currently being tested in 3 simultaneous studies
Clobazam – Approved for Lennox-Gastaut syndrome in other countries
AED’s recently approved by the FDA include Banzel, Lyrica, Sabril and Vimpat.
What Lies Ahead
Epilepsy treatments remain a dichotomy, both promising and frustrating. For example,
•Available medications have more than doubled in the last 10 years, yet the percentage of patients with retractable seizures has improved only slightly.
•There are many new drugs in the pipeline, yet there seems to be no breakthrough medication like Keppra was 10+ years ago.
•Pharmaceutical companies continue to commit resources to new AED’s, yet other conditions like Alzheimer’s Disease, pain, and Parkinson’s Disease receive much larger portions of R&D budgets.
•Therapeutic devices are a growing segment, yet remain a serious treatment for refractory patients as many require the surgical implant of medical hardware
On the positive side, the two-day Pipeline Conference presented a truly comprehensive view of medications and devices under development. Universities, venture capitalists, startups, non-profits and public companies focused on epilepsy can be surprisingly collaborative. Finally, non-profits play expanding, positive roles, with the Epilepsy Therapy Project, CURE and the Epilepsy Foundation all funding new research.
- D. Andrew Neff, Pipeline Event Attendee and Epilepsy Foundation Board Member