Tuberous Sclerosis Complex Takes Major Step With Epidiolex Approval

Martina Bebin, MD

The treatment landscape for patients with tuberous sclerosis complex (TSC) recently expanded in August, with the FDA approving a new indication for cannabidiol ([CBD] Epidiolex; GW Pharmaceuticals) for the treatment of seizures associated with TSC. The oral solution was approved for use in patients age 1 and older with TSC.

Epidiolex’s approval marks only the second FDA-approved treatment for TSC, which is associated with growth of benign tumors in the brain and other organs resulting in seizures, developmental delay, and behavioral problems. Martina Bebin, MD, professor of neurology and pediatrics, University of Alabama at Birmingham Epilepsy Center, understands the magnitude of the approval after practicing in neurology for over 20 years.

She sat down with NeurologyLive to discuss the approval, challenges patients with TSC face, and the novelty of CBD as a therapeutic. Bebin also touched on the importance of the expanded indication for patients at such an early age, as well as where we currently stand on prevention strategies.

NeurologyLive: What impact does the approval of CBD have on the way clinicians care for patients with TSC?

Martin Bebin, MD: The FDA approval of Epidiolex last month is very exciting, particularly for clinicians who care for patients with TSC because they have a very high seizure burden. About two-thirds of them develop drug-resistant epilepsy and it can be a very difficult condition to manage. Now, we have Epidiolex approved for TSC in a variety of seizure types, not just the focal seizures that were studied and identified in the trial, but also the researchers looked at generalized seizures and other types of generalized seizures. It’s really nice to have it approved in TSC because it only helps the numerous seizure types that patients with TSC have.

What sorts of challenges do patients with tuberous sclerosis complex face in comparison with other epilepsies?

The first thing is that it’s a genetic condition. In those patients, there’s 2 different genes that cause TSC, either TSC1 or TSC2. Interestingly, those patients with TSC2 have a much higher risk to develop epilepsy. One of the biggest windows of time for having high risk of seizure is within the first 3 years of life, and in particular the first year of life. By the age of 2, more than 80% will start having epilepsy. In tuberous sclerosis, you have tubers in the brain that are the primary generators of the seizures, which is a little bit different than some other types of epilepsies.

Can you discuss the novelty of CBD and the role it plays in the epilepsy community?

It’s been around for a long time now. Of all the compounds we’ve had, there are CBD formulations that you can get that have not taken the FDA route for drug approval process. As a clinician, I have much more confidence in a compound that has gone through the rigor of an FDA process that includes all the bars of safety and efficacy. It provides much more information in terms of guidance on how you can take care of a patient if you want to implement Epidiolex or CBD into their seizure management regimen.

The approval is indicated for those age 1 and older; what is the importance of treating patients with TSC at an early stage?

With Epidiolex being approved down to the age of 1, it can be very advantageous. You have that option to implement that in the regimen in a child that’s as young as a toddler. TSC is in somewhat of a unique position in that it is a genetic disorder. We have the capability to diagnose it prenatally, and that opens the opportunity for the children with TSC to be seen and followed very closely by a neurologist. It’s a very unique position of which, myself, as well as a group of other TSC researchers, are very interested in looking at. We want to identify children, particularly babies, before they even have their first seizure because the ultimate goal is being on the preventative side of epilepsy, which is where we’re headed. For now, it’s so nice to have another option that’s really gone through the rigor of the FDA process.

How far away from true prevention are we?

I’ve been practicing neurology for over 20 years and there has been a notable change in how clinicians’ practice, and it’s certainly within reach. We’re doing it now to be on the preventative side and early identification of patients with TSC. We have to figure out what impact we can have on early treatment. Not only how this impacts seizures, but does it impact their development, mainly because these children are at high risk for intellectual disability and autism. In our mind’s eye, the target is to find a cure. For many of the children I see, I think there’s great interest in their lifetime, probably in the next decade, that we can get there. The researchers in the test community are extremely motivated and creative thinkers are very enthusiastic about collaborating with our researchers and other disciplines. The basis of tuberous sclerosis is the mTOR pathway, which is so pivotal in so many systems within the body.

What are the next steps in treating patients with TSC? What are the current unmet needs?

At this point in time, a lot of emphasis has been placed, and is currently improving, on the early recognition and early identification of not only a patient to have the diagnosis of tuberous sclerosis, but the awareness of their risk for seizures and refractory epilepsy. To have Epidiolex as another option to treat this patient population is wonderful and welcomed. Not just that, but it also gives more options for parents who take care of their children as well.

How do you feel that this CBD product will impact future studies?

I know there’s a lot of enthusiasm and interest in not only how CBD or Epidiolex has impacted seizures, but to better understand its mechanism and what other potential benefits there might be from those CBD compounds. More and more information and better understanding of CBD and its utility in physiology is really emerging. We’re going to learn more and more as each year passes.

There’s been such an interest in the community with this approval. For parents or patients who are interested, definitely talk to your neurologist. Most TSC clinicians are certainly aware of Epidiolex, and it certainly may be an option for those who have not had the opportunity to try it in the past.

Transcript edited for clarity.