Epilepsy Market Grows, Widens in 2018

The treatment options for epilepsy seemingly grew exponentially in 2018—not only in bolstered pharmacotherapy, but in entirely new drug classes, new methods of administering care, and in new ways of leveraging technology to optimize treatment benefits.

Cannabidiol Approval Makes Waves

As many specialty fields continue to focus on patient-tailored medication, neurologists and clinicians addressing burdensome seizures in both pediatric and adult patients can feel assured knowing 2018 delivered nearly a dozen more treatment options for epilepsy and associated conditions.In June, the US Food and Drug Administration (FDA) approved a cannabis-derived drug for the treatment of 2 rare and severe forms of epilepsy. Cannabidiol oral solution (Epidiolex) was the first drug approved by the FDA containing a marijuana-derived, purified drug substance.

Epidiolex was approved for the treatment of seizures associated with Lennox-Gastaut syndrome and Dravet syndrome for patients 2 years of age and older. This was the first approved treatment for patients with Dravet syndrome. As of early November 2018, Epidiolex was made available in the US by prescription.

The FDA emphasized that cannabidiol does not cause any of the typical intoxication or the euphoria that is associated with tetrahydrocannabinol (THC), the primary psychoactive component of marijuana, and said that the approval was supported by careful testing and review.

“Controlled clinical trials testing the safety and efficacy of a drug, along with careful review through the FDA’s drug approval process, is the most appropriate way to bring marijuana-derived treatments to patients,” FDA Commissioner Scott Gottlieb, MD, said at the time of the approval.

Because of the strength of clinical studies supporting the cannabidiol application, prescribers and providers should have confidence in its “uniform strength and consistent delivery that support appropriate dosing” necessary for patients, Gottlieb explained.

The therapy’s approval wasn’t the first instance of it receiving a form of regulatory support this year. In April, an FDA advisory committee voted unanimously to support Epidiolex. The drug had previously been granted fast track designation to shorten the review process.

Research supporting cannabidiol oral solution for approval included a phase 3 trial that compared Epidiolex (10 mg/kg or 20 mg/kg) with placebo in adults and children with Lennox-Gastaut syndrome (n = 225).

Investigators found a 41.9% reduction in drop seizures in patients receiving a 20 mg/kg per day cannabidiol regimen, a 37.2% reduction with the 10 mg/kg per day cannabidiol regimen, and a 17.2% reduction with placebo (20 mg/kg cannabidiol vs. placebo, P = .005; 10-mg cannabidiol group vs. placebo, P = .002).

A study presented after the Epidiolex approval at the at the 2018 annual meeting of the American Epilepsy Society found a dose-dependent relationship between cannabidiol treatment and epileptic seizure reduction in children and adults.

Wider Approvals for Epilepsy

“There was a linear relationship between the cannabidiol dose and the plasma levels of the drug, and higher plasma levels were associated with a higher chance for improvement of the seizure rate,” Jerzy Szaflarski, MD, PhD, Director of the Division of Epilepsy in the Department of Neurology at the University of Alabama (UAB), Birmingham, explained to MD Magazine® at the conference.While Epidiolex made waves as a marijuana-based drug a handful of other treatments for epilepsy were approved in 2018, including stiripentol, everolimus tablets, brivaracetam, perampanel.

Stiripentol (Diacomit) was approved as only the second treatment for patients with Dravet syndrome. The drug is approved for use as an adjunct to clobazam in patients 2 years of age and older, but not as monotherapy.

The FDA also approved a treatment for another rare condition: tuberous sclerosis complex (TSC)-associated partial-onset seizures. Everolimus tablets for oral suspension (Afinitor Disperz) are the first US-approved drug for the rare genetic disorder that can cause seizures that are resistant to anti-epileptic medicines.

Brivaracetam (Briviact) received an expanded indication to include pediatric patients 4 years of age and older. The therapy is approved both as monotherapy and adjunctive therapy for the treatment of partial onset (focal) seizures.

Another supplemental NDA approval for pediatric patients with epilepsy was for perampanel (Fycompa). Perampanel was approved for the treatment of partial-onset seizures in patients 4 years of age and older. The therapy had previously been granted Priority Review.

Technology and Devices

Finally, the FDA has accepted a New Drug Application (NDA) for midazolam nasal spray for the acute treatment of seizure clusters. The treatment, previously granted Orphan Drug and Fast Track designations, may be approved in early 2019, bringing another needed option to the table for providers and patients with epilepsy.New devices made their way to the epilepsy market, as well. The Embrace smartwatch, a wearable device designed to track generalized tonic-clonic seizures through advanced machine learning, was approved by the FDA in February. The smaller, wearable device was designed by Empatica Inc. with the intention of modernizing clinical technology.

“We wanted to design the world's first medical device that could win a design award while being used as a lifesaving product,” Matteo Lai, BSc, MCs, chief executive officer and co-founder, said at the time of approval. “Patients actually love Embrace and are proud to wear it.”

A therapeutic device, Medtronic’s Deep Brain Stimulation (DBS) electrical pulse therapy, was also approved this year—for adjunctive reduction of partial-onset seizures in patients aged 18 years or older who are refractory to at least 3 antiepileptic medications.

The device brings the FDA a step closer to addressing what Stanford Epilepsy Center director and lead SANTE trial investigator Robert Fisher, MD, PhD called an unsolved problem: antiepileptic drug-refractory epilepsy.

“DBS therapy will now serve as an important new treatment option, including for people with poorly localized or multiple regions of seizure origin,” Fisher said at the time.

The future of greater epilepsy care may include more consideration to technological advances. Studies such as those conducted by EpiFinder, Inc. and the Mayo Clinic, and reported earlier this year, found the former company’s eponymous application is near 90% accuracy in predicting epilepsy syndrome or alternative diagnosis in susceptible patients.

As more devices reach the FDA, regulatory expectations could help to improve their clinical accuracy and capabilities.

“We fall into a clinical decision support tool as a part of digital health platforms,” EpiFinder co-founder and chief strategy officer Neel Mehta, MS, said. “However, we are working with our healthcare advisory council to make sure that our applications are in alignment per the required approval from the government.”

_{This article is part of MD Magazine's This Year In Medicine 2018 series. To read more from the series, check out the links below and follow us on Twitter at @MDMagazine.Finding and Treating the Young Hepatitis C Patient}

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