UHealth Launches New Deep Brain Stimulation Treatment for Epilepsy

A clinical team from the University of Miami Miller School of Medicine’s Comprehensive Epilepsy Center and the Department of Neurosurgery recently performed Florida’s second deep brain stimulation (DBS) surgery for a patient with intractable epilepsy. The new treatment, which was approved by the FDA in 2018, offers a new therapeutic strategy for patients whose epilepsy cannot be treated effectively by medications or resective surgery.

“This is an important step forward in our program,” said Andres M. Kanner, M.D., professor of clinical neurology, chief of the epilepsy division in the Miller School’s Department of Neurology, and director of the epilepsy center. “Many patients can potentially benefit from DBS, one of the types of neuromodulation therapy, which consists of sending electrical pulses to the anterior nucleus of the thalamus and from that structure, to electric circuits of the brain involved in the development of epileptic seizures.”

A pivotal study in the United States showed a significant decline in the frequency of seizures in 60 percent of 110 patients with previously uncontrolled epilepsy. The FDA has approved DBS for patients 18 years and older.

“While not curative, this therapy over time can yield a reduction of more than 50 percent in seizure frequency in about 60 to 70 percent of patients,” Dr. Kanner said. “Our center is the only facility in South Florida offering this option for safe and effective improvement in seizure frequency.” He noted that the Miller School center has received a level IV designation by the National Association of Epilepsy Centers for providing the most comprehensive evaluations and treatments for all forms of epilepsy.

Potassium Bromide Should be Considered for Treatment of Refractory Epilepsy, Study Says

Potassium bromide (KBr) can control certain types of epileptic seizures and should be considered as an option for the treatment of children with refractory epilepsy, a study says.

The findings of the study, “Potassium Bromide in the Treatment of Pediatric Refractory Epilepsy,” were published in the Journal of Child Neurology.

Dravet syndrome is a severe type of drug-resistant epilepsy that usually emerges during the first year of life and is characterized by seizures, cognitive deficits, and increased mortality.

In this study, a group of researchers from the Chiba Children’s Hospital in Japan set out to examine the efficacy and tolerability of KBr for the treatment of children with refractory epilepsy.

Treatment was found to be effective in more than half of the children diagnosed with generalized epilepsy (59.1%) and focal epilepsy (55.6%). In addition, KBr also led to significant improvements in seizure control among the two children who had been diagnosed with Dravet syndrome.

The treatment was more effective in children who had tonic seizures (72.2%), generalized tonic-clonic seizures (66.6%), or secondary generalized seizures (75.0%). KBr therapy was less effective among children who had focal seizures (46.2%), infantile spasms (20.0%), or myoclonic seizures (0%).

Adverse effects, which included drowsiness, excitement and skin rashes, were reported in 13 (31.0%) children participating in the study.

Zogenix Completes Enrollment in Phase 3 Trial of FINTEPLA® in Lennox-Gastaut Syndrome

Zogenix, Inc. announced that it has completed enrollment for, and randomized the last patient into the treatment period of, Study 1601, the Company’s Phase 3 clinical trial of its lead investigational therapy, FINTEPLA® (ZX008, fenfluramine), for the treatment of seizures associated with Lennox-Gastaut Syndrome (LGS), a severe and often treatment-resistant childhood-onset epilepsy.

“We have been extremely pleased with the rate of enrollment in this trial and look forward to the availability of top-line safety and efficacy data in the first quarter of 2020,” said Gail M. Farfel, PhD, Executive Vice President and Chief Development Officer of Zogenix.  “Based on the compelling data generated in the previously completed Phase 2 study, we believe this promising drug candidate has the potential to become an important new treatment option for the control of seizures in patients suffering from LGS.”

FINTEPLA for the treatment of LGS has previously been designated as an orphan drug by both the FDA and the European Medicines Agency.

Inhaled Alprazolam Rapidly Suppresses Epileptic Activity in Photosensitive Participants

OBJECTIVE: Treatment options for seizure clusters are limited; the need for easy-to-administer treatments remains. The Staccato system delivers drug deep into the lung via inhalation. In this phase 2a study, researchers investigated the ability of three different doses of Staccato alprazolam to suppress the electroencephalographic (EEG) photoparoxysmal response (PPR) compared with placebo in participants with photosensitive seizures.

METHODS: Adults (18-60 years) with a diagnosis and history of PPR on EEG with or without an epilepsy diagnosis were eligible to participate. Participants received Staccato alprazolam 0.5, 1.0, and 2.0 mg, and Staccato placebo (twice) in random order. Intermittent photic stimulation and clinical assessments were performed at one predose and seven postdose time points. The primary endpoint of the study was the change in standardized photosensitivity range (SPR) in participants receiving each dose of Staccato alprazolam.

RESULTS: Fifteen participants with a prior epilepsy diagnosis were screened; five were enrolled, randomized, and completed the study. All participants were white females with a mean (SD) age of 27.2 (6.8) years. All doses of Staccato alprazolam reduced the SPR at 2 minutes; the effect was sustained through 4 hours for the 0.5-mg dose and 6 hours for the 1.0- and 2.0-mg doses. The magnitude and duration of sedation and sleepiness were dose-related. Four participants (80%) experienced 1 or more adverse events (AE); none was severe or serious. Cough, diarrhea, dysgeusia, oral dysesthesia, sedation, and somnolence were experienced by two participants (40%) each.

SIGNIFICANCE: This proof-of-concept study demonstrated that Staccato alprazolam 0.5, 1.0, and 2.0 mg rapidly suppressed epileptiform activity in photosensitive participants with epilepsy. The adverse event [negative side effect] profile of Staccato alprazolam was similar to what has been reported for alprazolam for other indications. The results support further development of Staccato alprazolam as a rescue medication for the acute treatment of seizures.

The European Committee for Medicinal Products for Human Use Backs Generic Lacosamide UCB for Partial-Onset Seizures

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for the antiepileptic lacosamide UCB (UCB Pharma SA) for partial-onset seizures.

This was an informed consent application, which makes use of data from the dossier of a previously authorized medicine. The reference product for lacosamide UCB is Vimpat (UCB).

“Lacosamide UCB is indicated as monotherapy and adjunctive therapy in the treatment of partial-onset seizures with or without secondary generalization in adults, adolescents and children from 4 years of age with epilepsy,” the EMA said in a statement.

Lacosamide UCB will be available as a 10-mg/mL solution for infusion, a 10-mg/mL syrup, and film-coated tablets in strengths of 50 mg, 100 mg, 150 mg, and 200 mg. The most common side effects are dizziness, headache, diplopia, and nausea.

Zogenix Ready to Resubmit Fintepla for Rare Epilepsy to FDA

In April, the FDA issued a Refuse to File (RTF) letter to Zogenix for its New Drug Application (NDA) for Fintepla (fenfluramine hydrochloride). The drug was developed to treat seizures associated with Dravet syndrome, a rare form of epilepsy characterized by frequent and prolonged seizures.

The company at the time indicated the application, which was submitted in February, was not “sufficiently complete to permit a substantive review.” The FDA had two concerns, the first over non-clinical studies that were not submitted over chronic administration of the drug, and what Zogenix indicated as an incorrect version of a clinical dataset.

Now, the company announced that after its Type A meeting with the FDA on May 30, it plans to resubmit its NDA for Fintepla. Based on the meeting, the company will resubmit the NDA without the inclusion of the new chronic toxicity studies requested in the original RTF letter. In terms of the second issue, Zongenix ran a root cause analysis to explain the incorrect clinical dataset originally submitted and discussed that analysis with the agency.

“We are very pleased with the outcome of our meeting with the FDA and appreciate their thoughtful approach in considering the totality of the data from our drug development program, along with additional clinical and non-clinical literature that will be referenced in our re-submission,” stated Stephen J. Farr, president and chief executive officer of Zogenix. “We now have the clarity required to successfully resubmit our Fintepla NDA, which we will anticipate will occur in the third quarter.”

Drugs Used for Epilepsy May Increase Risk of Dementia, Study Shows

Scientists have long found a possible link between anticholinergic drugs and an increased risk of dementia.

A study published in the journal JAMA Internal Medicine suggests that the link is strongest for certain classes of anticholinergic drugs — particularly antidepressants such as paroxetine, bladder antimuscarinics such as oxybutynin, antipsychotics such as chlorpromazine or olanzapine and antiepileptic drugs such as oxcarbazepine [sold under the brand name Trileptal] or carbamazepine [sold under the brand name Tegretol among others].

Researchers wrote in the study that “there was nearly a 50% increased odds of dementia” associated with a total anticholinergic exposure of more than 1,095 daily doses within a 10-year period, which is equivalent to an older adult taking a strong anticholinergic medication daily for at least three years, compared with no exposure.

It has been well known that anticholinergic agents and confusion or memory issues are linked, but the new study investigated this association over a long period of time, said Dr. Douglas Scharre, director of the division of cognitive neurology at the Ohio State University Wexner Medical Center in Columbus, who was not involved in the study.

He encouraged any patients who might have questions about this association to talk to their physicians.

Encoded Therapeutics Bags $104M to Propel ‘Precision Gene Therapy’ for Dravet Syndrome

Encoded Therapeutics reeled in $104 million in series C cash to bankroll the development of its lead program: a precision gene therapy for Dravet syndrome, a rare form of epilepsy. The Bay Area biotech will also use the funds to push its preclinical programs and come up with new treatments for severe genetic disorders.

The company’s work is based on a platform designed to overcome hurdles it has identified in the gene therapy space. Gene therapies tend to work in one of three ways: They deliver a healthy copy of a faulty gene, introduce a new gene into the body or “knock out” a defective gene. But they can run into problems with cell selectivity, potency and the ability to control endogenous genes, Encoded CEO Karthik Ramamoorthi, Ph.D., told FierceBiotech.

“We’ve developed a series of technologies that are both computational and genomics- or sequencing-based that allow us to screen for and identify sequences in vivo that control where and when genes are able to be expressed,” Ramamoorthi said. “We take these sequences and place them in gene therapies—such as adeno-associated viruses (AAVs)—that allow us to control where the adeno-associated viruses are able to express the payload.”

Eisai Presents Data To Assess Seizure Freedom With FYCOMPA® Monotherapy In Newly Diagnosed Or Untreated Patients With Partial Onset Seizures

Results of the FREEDOM Study (Study 342) presented at the 33rd International Epilepsy Congress (IEC)- In a single-arm study, 63% of patients treated with FYCOMPA 4mg/day achieved seizure freedom at 26 weeks

Eisai Inc. announced results from its FREEDOM Study (Study 342), a Phase III open-label study conducted in Japan and South Korea evaluating the efficacy and safety of FYCOMPA® (perampanel) CIII as monotherapy in new onset or untreated patients with partial-onset seizures (POS). The data was presented at the 33rd International Epilepsy Congress (IEC) taking place in Bangkok, Thailand.

“Through research and development of compounds in our epilepsy franchise, Eisai is committed to shifting the conversation from seizure control to seizure freedom whenever possible. Results from this first investigation of FYCOMPA as monotherapy in patients with partial-onset seizures are an example of this shift,” said Lynn Kramer, MD, Chief Clinical Officer and Chief Medical Officer, Neurology Business Group, Eisai Inc. “Data from the FREEDOM study showed a seizure freedom rate of 63% with a 4mg/day dose of FYCOMPA as monotherapy in newly diagnosed or untreated  patients with POS.”

Seizure freedom for partial-onset seizures was achieved in 63% of patients (46/73) treated with FYCOMPA at Week 26 (95% CI: 50.9–74.0). Of those patients who had secondarily generalized seizures 65% (n=31/48) were convulsive seizure free. The most common adverse events (occurring in >5% of patients) out of 68 patients were dizziness (n=18 [26.5%]), nasopharyngitis (n=9 [13.2%]), somnolence (n=9 [13.2%]) and headache (n=7 [10.3%]).

CU Professor Helping Those with Severe Epilepsy

An approved epileptic drug to treat seizures has been modified by a University of Colorado Anschutz Medical Campus professor and is currently being used in a clinical trial in Australia for medically refractory epilepsy.

Tom Anchordoquy, PhD, professor at the CU Skaggs School of Pharmacy and Pharmaceutical Sciences, and Dan Abrams, MD, CEO of Cerebral Therapeutics, have developed a proprietary reformulated specialty pharmaceutical, which bypasses the blood-brain barrier using a chronic implantable infusion system, to improve the lives of patients with severe medically refractory epilepsy. The two have worked together for over a decade developing drug formulations to be injected directly into the brain where it is needed.

Cerebral Therapeutics is conducting a proof-of-concept study in adult patients at Australia’s University of Melbourne using its proprietary anti-epileptic specialty formulation via direct intracerebroventricular (ICV) administration. This proof-of-concept study has demonstrated potentially enhanced efficacy and reduced toxicity in patients with medically refractory epilepsy. Proceeds from the financing will be used to file an IND with the U.S. Food and Drug Administration (FDA) to initiate a Phase 2 clinical trial.