Striving for Full Seizure Control in Epilepsy, LGS, Dravet Syndrome

September 7, 2018

The director of the Epilepsy Program at the Banner University Medical Center spoke about the needs in patient populations with epilepsy.

Steven S. Chung, MD

The epilepsy treatment landscape has been an ever-evolving one, with new understandings and developments consistently reshaping the state of care.

Steven S. Chung, MD, the executive director and program chair of the Neuroscience Institute and director of the Epilepsy Program at the Banner University Medical Center, knows this better than most. With a history serving as a principal investigator on clinical trials and research projects concerning pharmacologic interventions for the condition, he’s seen the field evolve.

To provide further insight into the space, and specifically, the state of care for patients with rare forms of epilepsy such as Lennox-Gastuat syndrome and Dravet syndrome, Chung spoke with NeurologyLive in an interview.

NeurologyLive: For you, what is the current state of care for epilepsy and what still needs to be addressed?

Steven S. Chung, MD: Epilepsy is a very common disorder that affects more than 3 million Americans and that number has been increasing due to many factors, including the aging population. The aging population is more prone to develop stroke and brain tumor, infection, and trauma and so on, and these kinds of things are what causes seizures due to the damage or the lesions in the brain. The fastest growing, newly diagnosed epilepsy is actually in that older age group of 65 years and above. We’re expecting a lot more people will have epileptic seizures.

Having said that, we all strive to get full control with minimal adverse effects and without any significant adverse effects. Only about 70% of the time we can have full seizure control and the remaining 30% continue to have seizures in spite of new medications. In the epilepsy world, that strive to get that improvement in that 30% population continues. We have more than 27 medications out there now, but each one of them has a different usage, a different way of working, and different tolerability. Altogether, what we try to do is get as close as possible to that complete resolution or complete treatment of seizures. There are many different areas of need. If you could only write one sentence on unmet needs, it would be that not everyone is having full seizure control despite many medications.

What are the biggest developments being made in the space, in your experience?

There are several new things developing. One is in cluster seizures or the patients who have seizures back to back. What can we do without sending those patients to the emergency department? There is some development in rescue medications, so that’s one area. The second area is a different mechanism of action, or the combination of different mechanisms of action, that provides, possibly, a better benefit for the patients who failed on already existing medications. The third would be for a specific syndrome within epilepsy, such as a Dravet syndrome or Lennox-Gastaut syndrome (LGS), and several medications have been developed or studied for that purpose.

The fourth is the new understanding of why people even develop refractory epilepsy, so we’re not just using the bread and butter medications. Maybe we can fundamentally treat those patients who are in a severely refractory population with things such as immunotherapy. Immunomodulatory therapy has some play, whether it’s working through the tumor necrosis factor alpha or interleukin beta, and there has been some effort there to find a way to treat the more extremely or severely refractory population in epilepsy.

What’s been happening to improve rescue medications?

The benefit of them is obvious. The people who have cluster seizures or impending doom of having seizures, there’s something we can do. But these medications have to be quickly administered and quickly absorbed into the system so that 2 things can happen: They can stop the ongoing seizure progression, and hopefully we can prevent the next seizure after having one.

Classically, we’ve been using clonazepam or other benzodiazepines. The problem is that there’s no quick way to deliver the medication into the system, so a new concept would be the number one thing needed. How about, instead of swallowing the pill that’s going to take a while, use intranasal? You spray it into the nose and the mucus layer in the nose will absorb it very quickly, which sends the compound into the brain to suppress the seizure activities. An even quicker way would be infusing it into an IV as an outpatient or self-administration.

One way being studied is inhalation. If you inhale rather than sniff into the nose, the aerosolized compound gets into the lungs, and there is much quicker absorption. Medications that have been looked at are all in the class of benzodiazepines in this delivery system that’s more convenient for the patient and have a very quick absorption into the system. There have been 3 compounds that have been studied.

The second area of new medications are a bread-and-butter type of development. One medication that’s called cenobamate has been studied and completed phase III studies and showed quite a bit of promising efficacy for those patients who failed multiple medications in the past. Despite many other medications that have come out in the last 5 years, some of these are on track to possibly see daylight next year.

What has been the state of care for patients in specific populations, such as those with Lennox-Gastaut syndrome and Dravet syndrome?

We often times put those things in the same sentence, but they are quite different syndrome disorders. Dravet syndrome is a younger population and there are lots of severe types of seizures and cognitive challenges. Certain medications we know, such as sodium channel blockers, can worsen these types of seizures. In LGS, even though it can start early, it is usually diagnosed at age 5 to 8 years, and it’s a lifelong treatment. It’s a wide-spectrum disorder in terms of intellectual capacity as well as seizure severity and resistance to these medications.

The common ground for these 2 syndromes is what we call epileptic encephalopathy. The concept here is, not only do the patients have seizures, but they have such a severe type of seizure so frequently that the seizures may interfere with the development of the brain. That kind of necessitates a more aggressive and more appropriate treatment early on, rather than to keep waiting and fussing with the different medications. Both of them are quite severe and refractory—very refractory—to existing medications.

Specifically, for LGS, we do have FDA-approved medications. Medications such as topiramate, levetiracetam, lamotrigine, clobazam, and rufinamide are the drugs that have clinical studies or have been approved for LGS. However, for Dravet syndrome, there was no real medication that was specifically studied and approved for that need until recently, CBD, or cannabidiol, the first cannabinoid-derived medication, not only for LGS, but for Dravet syndrome. It’s not available yet, but it’s a newly developed and approved medication.

Transcript edited for clarity.