First Prescription Formulation of Cannabidiol (CBD) Approved for Lennox-Gastaut Syndrome

The LGS Foundation is pleased to announce that the US Food and Drug Administration (FDA) has approved EPIDIOLEX® (cannabidiol / CBD) for the treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients two years age or older. EPIDIOLEX® is the first prescription pharmaceutical formulation of highly purified CBD and the first in its class of anti-epileptic drugs.

“Today’s announcement gives individuals with Lennox-Gastaut Syndrome and their families much-needed hope,” says LGS Foundation Executive Director Christina SanInocencio. “Lennox-Gastaut syndrome is a devastating form of epilepsy and despite currently available FDA-approved medications and a poly-therapy approach to treatment, the majority of individuals with LGS will continue to have life-long, debilitating seizures, along with cognitive impairment and abnormal waves on the EEG (electroencephalogram).”

Cannabidiol (CBD) is a compound derived from the cannabis plant that does not produce a “high” and has been an increasing focus of medical research in epilepsy. Recently, study results from the clinical trial of EPIDIOLEX® published in the New England Journal of Medicine showed to significantly reduce the number of seizures in patients with Lennox-Gastaut Syndrome.

Along with the FDA’s approval for EPIDIOLEX® for seizures associated with Lennox-Gastaut syndrome, the approval is also indicated for another form of rare epilepsy that begins in childhood called Dravet syndrome.

The adult motor phenotype of Dravet syndrome is Associated with Mutation of the STXBP1 Gene and Responds Well to Cannabidiol Treatment

Dravet syndrome is a terrible disease generally caused by mutations of the SCN1A gene. Recently others genes such as STXBP1 have been involved in the pathogenesis of the disease. The STXBP1 mutation in patients with Dravet Syndrome may additionally causes several parkinsonian features usually attributed to carriers of the SCN1A mutation. Management continues to be difficult; that is why Cannabidiol emerged as valid option for treatment of this condition.

Inadequate Regulation Contributes to Mislabeled Online Cannabidiol Products

Researchers from the University of Pennsylvania, Veterans Affairs San Diego, RTI international, Americans for Safe Access, Palo Alto University, and Johns Hopkins University analyzed the content of 84 cannabidiol (CBD) products purchased on the internet and compared the results to their advertised concentrations. Products were mislabeled with 26% containing less CBD than labeled and 43% containing more, indicating a high degree of variability and poor standardization of online products.

Notably, the oil-based products were more likely to be accurate (45% compared to 25% for tincture and 12.5% for vaporization liquid) and had a smaller percentage of deviation. Oil based products also had a higher range of concentration. In addition to CBD mislabeling, ?-9-tetrahydrocannabibolic acid (THC) was detected in 21% of samples. This study also notes that products containing THC could have sufficient enough concentrations to produce intoxication in children.

Results of Phase 3 Study of Cannabidiol Oral Solution in Lennox-Gastaut Syndrome Show Significant Reduction in Drop Seizures

GW Pharmaceuticals plc along with its U.S. subsidiary Greenwich Biosciences announced the publication of results from a Phase 3 study of cannabidiol oral solution (Epidiolex®) in patients with Lennox-Gastaut syndrome (LGS), a rare, severe and difficult-to-treat form of childhood-onset epilepsy. In this study, both evaluated doses of cannabidiol oral solution significantly reduced the monthly frequency of drop seizures compared to placebo in highly treatment-resistant patients when added to existing treatment.

“This publication in The New England Journal of Medicine marks another landmark for GW Pharmaceuticals with data again published by a top-tier, peer-reviewed journal. It offers further evidence for cannabidiol oral solution as a potential future treatment option for patients with this devastating condition,” said Justin Gover, GW’s Chief Executive Officer. “We are now in the latter stages of the FDA’s review of our New Drug Application and look forward to a decision from FDA in late June. If approved, we expect to make this important potential new medicine available to U.S. patients with LGS in the second half of the year.”

FutureNeuro and GreenLight Medicines Partner to Develop Treatments for Epilepsy

A new partnership between FutureNeuro, the SFI Research Centre for Chronic and Rare Neurological diseases based at RCSI, and GreenLight Medicines, an indigenous Irish biopharmaceutical company, has been formed to develop new cannabis-based treatments for drug resistant epilepsies, and in particular, childhood epilepsies.

The research will explore how cannabidiol (CBD) and other non-psychoactive molecules from the cannabis plant can reduce seizures. It will also look at optimizing the effectiveness of this new approach to treat epilepsy.

“This project has strong alignment with FutureNeuro’s strategic goal to bring novel treatments to patients in Ireland with difficult to control epilepsy” said Professor David Henshall, academic supervisor on the project and FutureNeuro Director. [Dr. Henshall is a former CURE grantee]

Dr. Colin Doherty, National Clinical Lead for Epilepsy and a Principal Investigator at the FutureNeuro Centre said, “The use of cannabis to treat epilepsy offers a tantalising new horizon for severe disabling seizures. The mechanism by which CBD exerts its antiepileptic effects is currently unknown, and this impactful research will help to provide clinical evidence of its long-term efficacy, as well as data on any long-term side effects.”

Epilepsy Research Findings: May 2018

This month I would like to share with you several promising treatment and diagnostic advances, and research discoveries. The FDA recently recommended supporting the approval of the New Drug Application for cannabidiol-based drug Epidiolex and also approved Medtronic’s deep brain stimulation therapy for drug-resistant epilepsy. Recent research has also provided the promise of new genetic insight for children with epileptic encephalopathy, and has brought us closer to understanding how to repair a “leaky” blood-brain barrier associated with epilepsy. In contrast to these exciting results, we have also learned that individuals with epilepsy are at an increased risk of dying from suicide and accidents, and a new study has highlighted the high direct costs associated with epilepsy for children with the disorder.

Summaries of all highlighted studies follow below. I’ve organized the findings into four categories: Treatment Advances, Diagnostic Advances, Research Discoveries, and Also Notable.

TREATMENT ADVANCES

GW Pharmaceuticals and U.S. Subsidiary Greenwich Biosciences Announces FDA Advisory Committee Unanimous Recommendation of Support for Epidiolex

GW Pharmaceuticals plc, along with its U.S. subsidiary Greenwich Biosciences, announced that the Peripheral and Central Nervous System Drugs Advisory Committee of the U.S. Food and Drug Administration unanimously recommended supporting the approval of the New Drug Application (NDA) for the investigational cannabidiol oral solution (CBD), also known as Epidiolex®, for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) and Dravet syndrome in patients two years of age and older. If approved, Epidiolex would be the first pharmaceutical formulation of purified, plant-based CBD.

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Medtronic Receives FDA Approval for Deep Brain Stimulation Therapy for Medically Refractory Epilepsy

Medtronic plc, the global leader in medical technology, announced that the U.S. Food and Drug Administration has granted premarket approval for Medtronic’s Deep Brain Stimulation (DBS) therapy as adjunctive treatment for reducing the frequency of partial-onset seizures in individuals 18 years of age or older who are refractory or drug-resistant to three or more antiepileptic medications. DBS therapy for epilepsy delivers controlled electrical pulses to a target in the brain called the anterior nucleus of the thalamus, which is part of a network involved in seizures.

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Zynerba Pharmaceuticals Announces Twelve Month Data from STAR 2 Study in Patients with Focal Seizures

Zynerba Pharmaceuticals, Inc reported new longer term open label clinical data from its STAR 2 Study in patients with focal seizures. “The data continues to suggest that focal seizures may be reduced with longer-term exposure to transdermally-delivered CBD,” said Dr. Liza Squires, Zynerba’s Chief Medical Officer. “In this population of patients, the use of ZYN002 for an additional 12 months in STAR 2 was well tolerated and appeared to result in clinically meaningful seizure reductions both across and within the originally randomized STAR 1 groups.”

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Zynerba Pharmaceuticals Initiates Open-Label Phase 2 Trial of ZYN002 in Developmental and Epileptic Encephalopathies

Zynerba Pharmaceuticals announced that it has initiated the Phase 2 BELIEVE 1 clinical trial, an open label study to assess the safety and efficacy of ZYN002 administered as a transdermal gel to children and adolescents with developmental and epileptic encephalopathy.

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DIAGNOSTIC ADVANCES

New Testing Provides Better Information for Parents of Children with Epileptic Encephalopathy

Advances in genetic testing offer new insights to parents who have a child with a rare but serious form of epilepsy, epileptic encephalopathy. New ways of sequencing the human genome mean geneticists and genetic counselors have much more to say to parents who wonder if future children might carry the disease, says Dr. Heather Mefford, Associate Professor of Pediatrics (genetic medicine) at University of Washington School of Medicine and Deputy Scientific Director of the Brotman Baty Institute for Precision Medicine, co-senior author of findings published in the New England Journal of Medicine.

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RESEARCH DISCOVERIES

Repairing a Leaky Blood-Brain Barrier in Epilepsy

In a study of rodent brain capillaries published in the Journal of Neuroscience, Björn Bauer and colleagues identified a seizure-triggered pathway that contributes to blood-brain barrier dysfunction in epilepsy. The blood-brain barrier is a filtering mechanism that lets nutrients into the brain but keeps toxins out. Understanding how a “leaky” blood-brain barrier can lead to seizures is necessary to develop strategies to plug the leak.

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Hope for New Treatment of Severe Epilepsy

Researchers at Lund University in Sweden succeeded in reducing epileptic activity in the hippocampus. In many severe cases of epilepsy, this is the part of the brain where epileptic seizures start. The researchers used a method known as chemogenetics, which enables them to reduce activity in the specific areas and nerve cells involved in an epileptic seizure, whereas other parts and cells in the body remain unaffected. This is in contrast to current drugs that affect more or less all parts and cells of the body, potentially leading to side-effects.

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Epilepsy Does Not Impact Likelihood of Pregnancy

Women with epilepsy, without previous infertility and related disorders, were as likely to conceive as their counterparts without epilepsy, according to findings recently published in JAMA Neurology. Dr. Page B. Pennell and colleagues found that 60.7% of women with epilepsy became pregnant versus 60.2% of the control group without epilepsy.

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Increased Risk of Suicide and Accidental Death Found for People with Epilepsy

A new study has shown that people diagnosed with epilepsy in England and Wales are at increased risk of dying from suicide and accidents. Though the risks of dying from suicide and accidents for people with epilepsy are low in absolute terms (0.3-0.5%), they are higher than in people without epilepsy, says Dr. Hayley Gorton from The University of Manchester.

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ALSO NOTABLE

What Modern Day Challenges Affect Epilepsy Treatment?

Researchers recently published an article in The Lancet Neurology discussing the difficulties facing seizure detection in patients with epilepsy. In a recent study, Christian Elger and Christian Hoppe determined that a key challenge facing patients is that over 50% of patients under-report the number of seizures they experience, which has a serious impact on how well doctors are able to determine what treatments are most suitable for them. This also calls into question much of the previously published research on epilepsy treatments.

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Study Finds a High Direct Cost of Epilepsy in Children

A study of children aged 17 years using data from the Medical Expenditure Panel Survey-Household Component found that medical expenditure among children with epilepsy is high. The high expenditure is essentially driven not only by inpatient expenditure but also by home healthcare, outpatient, and medication healthcare expenditures.

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May CURE Update: Epidiolex, Sabril, and Epilepsy Education Events

I was recently interviewed by Business Insider about the FDA’s review of a potential new anti-epilepsy drug, Epidiolex. In Phase III clinical trials, 44% of patients with Lennox-Gastaut Syndrome (LGS) and 43% of patients with Dravet syndrome who used Epidiolex saw a 50% or greater reduction in their seizures compared to 24% and 27% of participants who took the placebo.

Epidiolex could be the first drug derived from cannabidiol (CBD) to gain FDA approval. Unlike THC, one of the other components in marijuana, cannabidiol is not an intoxicant. So, Epidiolex does not have hallucinogenic effects. The FDA is expected to make its final decision about Epidiolex in June.

In other news: CURE is announcing the expansion of its Day of Science event; CURE is urging insurance companies to maintain reasonable access to Sabril; and you can now support CURE while drinking your morning cup of coffee. Read on….

 

DAY OF SCIENCE IS EXPANDING TO SIX LOCATIONS!

CURE’s 2018 Day of Science events kick-off in June. At these free events, you can learn about cutting-edge epilepsy therapies and treatments, via:

  • Q&A sessions with panels of epilepsy physicians
  • Small-group roundtable discussions led by experts

 

You’ll also get the opportunity to engage with others in the epilepsy community.

Registration is now open for the Days of Science in:

 

Stay tuned for details about CURE’s Days of Science in the following cities:

  • Houston
  • Los Angeles
  • Miami
  • Raleigh-Durham

 

Interested in volunteering? Please contact the Day of Science team at DOS@CUREepilepsy.org or (312) 255-1801.

Zynerba Pharmaceuticals Announces Twelve Month ZYN002 Data from STAR 2 Study in Patients with Focal Seizures at the 2018 Annual Meeting of the American Academy of Neurology (AAN)

Zynerba Pharmaceuticals, Inc., a clinical-stage specialty neuropsychiatric pharmaceutical company dedicated to developing and commercializing innovative pharmaceutically-produced transdermal cannabinoid treatments for rare and near-rare neurological and psychiatric disorders with high unmet medical needs, is reporting new longer term open label clinical data today in the Emerging Science session of the 2018 Annual Meeting of the American Academy of Neurology (AAN) in Los Angeles, CA.

In a poster presentation entitled, “Transdermal Cannabidiol (CBD) Gel for the Treatment of Focal Epilepsy in Adults” (poster P4.468), Dr. John Messenheimer presents additional data from ongoing STAR 2 (Synthetic Transdermal CAnnabidiol for the TReatment of Epilepsy) 24-month open label extension study evaluating ZYN002 cannabidiol (CBD) transdermal gel in adult patients with focal seizures. The presentation includes data through twelve months of open label exposure to ZYN002.

The key findings include that responses to ZYN002 in the STAR 2 open label extension, as measured by reductions in focal seizures from the baseline period of STAR 1, are associated with continued treatment with ZYN002. In addition, ZYN002 was shown to be well tolerated through 12 months of treatment in STAR 2.

“These data continue to suggest that focal seizures may be reduced with longer-term exposure to transdermally-delivered CBD,” said Dr. Liza Squires, Zynerba’s Chief Medical Officer. “In this population of patients, the use of ZYN002 for an additional 12 months in STAR 2 was well tolerated and appeared to result in clinically meaningful seizure reductions both across and within the originally randomized STAR 1 groups. These data continue to provide insight into the potential for ZYN002 in certain epilepsies, and we look forward to initiating a Phase 2b study in adult refractory focal seizures in the second half of 2018.”

GW Pharmaceuticals and U.S. Subsidiary Greenwich Biosciences Announces the Unanimous Positive Result of FDA Advisory Committee Meeting for First Plant-Based Pharmaceutical [CBD] Treatment for Seizures in Patients with Two Rare, Severe Forms of Epilepsy

GW Pharmaceuticals, a biopharmaceutical company focused on discovering, developing and commercializing novel therapeutics from its proprietary cannabinoid product platform, along with its U.S. subsidiary Greenwich Biosciences, today announced that the Peripheral and Central Nervous System Drugs Advisory Committee of the U.S. Food and Drug Administration (FDA) unanimously recommended supporting the approval of the New Drug Application (NDA) for the investigational cannabidiol oral solution (CBD), also known as Epidiolex, for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) and Dravet syndrome in patients two years of age and older. If approved, Epidiolex would be the first pharmaceutical formulation of purified, plant-based CBD, a cannabinoid lacking the high associated with marijuana, and the first in a new category of anti-epileptic drugs (AEDs). This public meeting was presented live through FDA’s website.

LGS and Dravet syndrome, which develop in childhood, are devastating forms of epilepsy with high morbidity and mortality rates and a significant burden on families and caregivers. More than 90% of patients with LGS or Dravet syndrome have multiple seizures per day, which puts them at constant risk for falls and injury. Physicians who treat LGS and Dravet syndrome patients struggle to reduce the sheer volume of dangerous seizures with currently available therapies. If approved, Epidiolex would be the first-ever FDA-approved medicine for Dravet syndrome patients.

“We are pleased by the Advisory Committee’s unanimous recommendation to approve Epidiolex, which would provide an important treatment option for patients with LGS and Dravet syndrome, two of the most severe and treatment-resistant forms of epilepsy,” said Justin Gover, GW’s Chief Executive Officer. This favorable outcome marks an important milestone in our company’s unwavering commitment to address the significant unmet need for patients with LGS and Dravet syndrome and our resolve to study Epidiolex under the highest research and manufacturing standards. We look forward to our ongoing discussions with the FDA as it continues to review the Epidiolex NDA.

A Powerful Drug Derived from Marijuana Just Got a Major Green Light on its Way to FDA Approval

Business Insider – An experimental drug derived from cannabis to treat epilepsy is on the brink of becoming the first of its kind to win US government approval.

On Thursday, a panel of outside experts convened by the Food and Drug Administration voted unanimously in favor of the drug’s safety and effectiveness. Their recommendation will play a key role in the FDA’s approval decision for the drug, which is made by GW Pharmaceuticals.

If the FDA gives final approval — a decision is expected in June — the new drug would be sold under the name Epidiolex as a syrup. It would be the first drug whose active ingredient is cannabidiol, the compound in marijuana thought to be responsible for many of its therapeutic effects.

Cannabidiol, or CBD, doesn’t contain THC, marijuana’s main psychoactive ingredient, and is not linked with euphoria or the drug’s characteristic high. CBD appears to help reduce seizures, at least in two of the hardest-to-treat forms of epilepsy, known as Lennox-Gastaut syndrome and Dravet syndrome. That’s according to two large clinical trials the FDA considered Tuesday ahead of the vote.

GW Pharma’s long road to FDA approval

In the absence of a research-backed drug, some desperate parents of children with epilepsy have turned to CBD oils and other CBD-based products at dispensaries — but most of those are not heavily regulated.

Laura Lubbers, the chief scientific officer of a nonprofit called Cure that funds epilepsy research, told Business Insider her group saw GW’s drug as a “long-awaited” treatment. That’s especially true for patients who haven’t responded to other drugs.

“What’s different with this drug is that this is a well-studied and well-controlled product,” Lubbers said.

Because GW Pharmaceuticals was able to show that its product addresses a critical need, it was able to apply for a designation to fast-track the Food and Drug Administration’s often protracted approval process.

One clinical trial of the drug looked at its effects in 225 young people with Lennox-Gastaut syndrome. The researchers split the study participants into groups and gave them either a high dose of the drug, a low dose, or a placebo for 14 weeks. The results were presented at an American Academy of Neurology meeting last year, and they showed that participants in the high-dose group saw their seizure occurrence drop by 42%. Those given the low dose saw a decrease of roughly 37%. By comparison, those given the placebo saw only a 17% reduction in seizure occurrence.

The second trial, the results of which were published in May 2017 in the New England Journal of Medicine, looked at 120 children with Dravet syndrome. Half were given the drug, and half received a placebo. Forty-three percent of the participants given the drug saw their seizures reduced by half, and 5% stopped having seizures entirely. The group given the placebo saw barely any improvement.

The FDA vote and the future of cannabis-derived drugs

While Epidiolex would be the first cannabidiol-based drug to land FDA approval, the agency has already given the green light to other drugs that contain a lab-made version of THC. Sold under the brand names Marinol and Syndros, the drugs are designed to treat some negative side effects of chemotherapy and AIDS, such as nausea, loss of appetite, and weight loss.

In its public meeting on Thursday, a panel of outside scientists convened by the FDA decided that Epidiolex was safe and effective. Their unanimous vote serves as a recommendation that will be considered when the final decision on whether to approve the drug is made.

“This is clearly a breakthrough drug for an awful disease,” John Mendelson, a panel member and senior scientist at the Friends Research Institute, said after the vote.

Epidiolex would be designed to treat only two types of epilepsy, so FDA approval would mean the drug would be prescribed for a small group of patients. But medical professionals could technically prescribe it “off-label” for other conditions as well. (The anesthetic ketamine, for example, may be prescribed this way for some hard-to-treat forms of depression.)

“We would expect that once this is approved as a drug it’s quite likely this will be tried in other populations off-label so it has a big opportunity to affect others,” Lubbers said.

According to the Centers for Disease Control and Prevention, epilepsy affects more than 3.4 million Americans. Though GW Pharma’s current drug focuses only on two rare types of the condition, the company has said it is exploring treatments for various other forms of epilepsy, too.

If this initial drug gets the green light, that approval will likely galvanize new research into other marijuana-based drugs as well.