Second Phase 3 of Dravet Drug Completes Enrollment

Zogenix, Inc. announced on January 31st that the last patient has been randomized into the treatment period of Study 1504, its second Phase 3 clinical trial evaluating ZX008 (low-dose fenfluramine) as an adjunctive treatment for seizures in children and young adults with Dravet syndrome.

At the 71st American Epilepsy Society (AES) Annual Meeting in December, positive safety and efficacy data from the company’s Study 1 trial, exhibiting the drug’s ability to achieve a clinically meaningful benefit in the same indication, were presented.

Dravet syndrome is a pediatric epilepsy disorder in which a wide variety of seizure types plague the patient, and the condition is often associated with a high mortality rate. It typically begins in the first year of life of an otherwise healthy infant, and those affected can also experience developmental delays, and, at present, there aren’t any approved orphan drugs to treat the condition.

“The completion of patient randomization in Study 1504 represents another significant achievement in our ZX008 Phase 3 development program in Dravet syndrome,” said Stephen J. Farr, Ph.D., President and CEO of Zogenix in a press release. “We expect to announce top-line data from this study in the second quarter of this year. The data generated to date from the Phase 3 clinical program have further strengthened our confidence in the potential of ZX008 to become an important treatment option for the control of seizures in patients suffering from Dravet syndrome, a rare and catastrophic form of epilepsy.”

Graduate student uses AI to advance epilepsy research

Artificial intelligence may be the next great medical tool for those with epilepsy, according to a research project done by Ph.D candidate Yogatheesan Varatharajah.

His research with AI resulted in a technique that can identify the brain regions that generate seizures, without requiring the inspection of actual seizures.

“While there is a lot of skepticism about whether artificial intelligence has a negative impact on humanity, we firmly believe that AI can be used to make mankind stronger and our work is a perfect example of that,” Varatharajah said.

Varatharajah’s technique helps forego the manual way to find these regions, which is done through electroencephalograms (EEG). The EEG test is a way for epileptologists, neurologists specializing in epilepsy, to record information from brain regions by attaching small, flat metal discs (electrodes) to your scalp.

“Later we found out that we need not even record seizures, and only non-seizure recordings can be sufficient to achieve accurate identification of seizure-generating regions,” Varatharajah said. “This was even more exciting because it has the potential to transform the way epilepsy surgery is currently performed.”

Corpus Callosotomy Can Help Reduce Seizures in Patients with Refractory Epilepsy Following Vagal Nerve Stimulation

According to news originating from Lebanon, New Hampshire, “Vagal nerve stimulation (VNS) and corpus callosotomy (CC) have both been shown to be of benefit in the treatment of medically refractory epilepsy. Recent case series have reviewed the efficacy of VNS in patients who have undergone CC, with encouraging results.”

The research, “Efficacy and safety of corpus callosotomy after vagal nerve stimulation in patients with drug-resistant epilepsy,” concluded: “The authors demonstrate that CC can help reduce seizures in patients with medically refractory epilepsy following VNS, particularly with respect to drop attacks. “

New genetic test can predict adverse reactions to epilepsy drug

A study led by researchers at RCSI (Royal College of Surgeons in Ireland) has identified a new genetic test that can be used to predict if a patient with epilepsy will develop an adverse reaction to a common anti-epileptic drug. The finding will help inform doctors to prescribe the safest and most beneficial treatment for patients with epilepsy.

The study, “Genetic variation in CFH predicts phenytoin-induced maculopapular exanthema in European-descent patients,” is published in the journal Neurology.

The research has identified a genetic factor that can be used to predict whether a patient with epilepsy will develop a rash in reaction to a common anti-epileptic drug called phenytoin. Phenytoin is used worldwide and is the most commonly prescribed anti-epileptic drug in developing countries.

Dr. Mark McCormack of the Department of Molecular and Cellular Therapeutics, RCSI, and first author on the paper commented: ‘Our finding will make it easier for clinicians to predict a troublesome rash which occurs as an allergic reaction to the drug phenytoin. Adverse reactions can sometimes cause more harm to patients than seizures and patients may stop taking otherwise useful drugs as a result of the side-effects. Through genetic testing we can now estimate a patient’s risk prior to placing them on phenytoin.’

Professor Gianpiero Cavalleri, Associate Professor in Human Genetics at RCSI and the FutureNeuro SFI Research Centre, coordinated the study. ‘This work represents a step towards more holistic, personalized care of epilepsy by improving patient safety and targeting the right drug to the right patient,’ Professor Cavalleri said.

New Apple Watch App Uses Algorithm to Detect Seizures & Alert Providers

Smart Monitor, a Silicon Valley, CA-based provider of clinically validated solutions for the management of complex chronic conditions has announced the launch of SmartWatch Inspyre for the Apple Watch.  The new Apple Watch app uses a unique algorithm to recognize a wearer’s repetitive shaking movements, similar to those caused by convulsive seizures.

Designated family members and care providers are alerted upon onset of these movement patterns so they can intervene in a timely manner to maximize safety of their loved one. The episodic data is captured in a secure HIPAA-compliant cloud for review and analysis.

SmartWatch Inspyre users can also summon help with the push of a button. Alerts can be sent to any phone, anywhere, and detailed reports of each event can be securely accessed for later review with physicians.

“We are pleased to be able to offer Inspyre on the Apple Watch,” said Anoo Nathan, CEO in a statement. “This really is a game changer for patients and families alike. Inspyre enhances the safety and autonomy of people prone to seizures while providing peace of mind for families and loved ones.

Cannabidiol helps reduce seizures in people with severe form of epilepsy, study suggests

A key cannabis compound helped to reduce the number of drop seizures in patients with a severe form of epilepsy, newly published results of a clinical trial suggest.

The study, published by The Lancet, suggests that cannabidiol, alongside other anti-epilepsy treatments, reduced drop seizures in those who suffer from Lennox-Gastaut syndrome.

Drop seizures involve sudden falls due to loss of muscle tone. Lennox-Gastaut is a severe, lifelong form of epilepsy involving frequent seizures and cognitive impairment. The syndrome causes about one to four per cent of childhood epilepsy cases, researchers say.

In the 14-week clinical trial, the frequency of seizures was reduced in those who took a pharmaceutical formulation of cannabidiol. But researchers say the long-term efficacy and safety of the cannabis compound, as well its interaction with other epilepsy drugs, still need to be studied and confirmed.

The study’s lead author, Dr. Elizabeth Thiele, a neurologist who specializes in pediatric epilepsy at the Massachusetts General Hospital, said she and her colleagues are “pleased that our study has potentially found an additional option to add to patients’ existing treatment to reduce drop seizures.” In a news release, she noted that “it’s important to highlight that the drug used in this trial is a pharmaceutical formulation, and not medical marijuana.”

Brivaracetam Clinical Trial: A Study to Evaluate the Pharmacokinetics, Safety, and Tolerability

The purpose of the Brivaracetam Clinical Trial is to evaluate the pharmacokinetics (PK), safety, and tolerability of brivaracetam (BRV) administered intravenously (iv) in subjects between 1 month and 16 years of age with epilepsy.

Eligibility Criteria

Inclusion Criteria:

  • Male or female from >= 1 month to < 16 years of age. For subjects who are < 1 year from birth and who were preterm infants, the corrected gestational age should be used for this entry requirement
  • Weight >= 3 kg (6.6 lbs)
  • Diagnosis of epilepsy
  • Acceptable candidate for venipuncture and intravenous (iv) infusion
  • Treatment with >=1 anti epileptic drug (AED; including BRV) without a change of dose regimen for at least 7 days prior to Screening
  • No treatment with vagus nerve stimulation (VNS), OR the subject is being treated with VNS and the settings have been constant for >=7 days prior to Screening
  • For female subjects: not of childbearing potential, OR of childbearing potential and not sexually active/negative pregnancy test, OR of childbearing potential and sexually active/negative pregnancy test/uses medically acceptable contraceptive methods

 

Exclusion Criteria:

  • Subject has previously received iv Brivaracetam (BRV) in this study
  • Subject is being treated with BRV at a dose >5mg/kg/day (rounded) or >200mg/day for subjects with body weights >40kg
  • Subject requires or is likely to require a change in concomitant antiepileptic drug(s) (AED[s]), dose of concomitant AED(s), or formulation of AED(s) during the 7 days prior to the intravenous (iv) pharmacokinetic (PK) Period
  • Subject is likely, in the opinion of the Investigator, to require rescue medication during the Initiating Oral BRV (IOB) Treatment or iv PK Periods
  • Subject has experienced generalized convulsive status epilepticus in the 28 days prior to Screening or during the Screening Period

Delayed Treatment Worsens Outcomes in Children with Status Epilepticus

Delayed first-line benzodiazepine treatment is independently associated with major adverse outcomes in children with status epilepticus (SE), according to a JAMA Neurology study. The results raise the question as to whether poor outcomes could, in part, be prevented by earlier administration of treatment.

Patients in the status epilepticus study were admitted with refractory convulsive SE to 11 pediatric tertiary hospitals in the United States and stratified into two groups — those who received timely first-line benzodiazepine (i.e., given within less than 10 minutes of seizure onset); and those who received treatment within 10 or more minutes.

The status epilepticus study associated an untimely treatment with a higher frequency of death, use of continuous infusions, longer convulsion duration, and more frequent hypotension. These findings may change the perception of acute seizure and status epilepticus treatment, tentatively converting it into an extremely time-sensitive emergency that is similar to stroke or other cardiovascular events.

Brain training: 45% of patients demonstrated a reduction in seizures of 50% or more

Dr. Nagai’s research found that training patients to increase their levels of alertness helped them to become better at calming their brain and reducing seizures.

Forty patients with drug-resistant temporal lobe epilepsy, aged 18 to 70, were recruited for a controlled trial from three screening centres. Some 45 percent of patients demonstrated a reduction in seizures of 50 percent or more. Dr. Nagai said: “Our clinical study provides evidence for autonomic biofeedback therapy as an effective and potent behavioural intervention for patients with drug-resistant epilepsy… This approach is non-pharmacological, non-invasive and seemingly side-effect free.”

FDA Review: Clobazam Oral Soluble Film for Treating Lennox-Gastaut Syndrome

The U.S. Food and Drug Administration has accepted for review a New Drug Application for clobazam Oral Soluble Film (clobazam OSF) for adjunctive treatment of seizures associated with Lennox-Gastaut syndrome in patients two years of age or older. The target date for completion of the FDA review is the third-quarter of 2018.

Clobazam OSF is administered using Aquestive’s PharmFilm drug delivery technology. Similar in size and thickness to a stamp, Aquestive’s PharmFilm dissolves instantly after being placed on the tongue and can be administered without water.

Two multicenter controlled studies were conducted to evaluate the bioequivalence of clobazam OSF with clobazam tablets, a benzodiazepine currently on market, at the same dosage strengths. Based on the studies, clobazam OSF was demonstrated to be bioequivalent to clobazam tablets and have comparable safety.