Posts Tagged Epidiolex

[Abstract + References] Pharmacological and Therapeutic Properties of Cannabidiol for Epilepsy

Abstract

Cannabidiol (CBD) is a major active component of the Cannabis plant, which, unlike tetrahydrocannabinol (THC), is devoid of euphoria-inducing properties. During the last 10 years, there has been increasing interest in the use of CBD-enriched products for the treatment of epilepsy. In 2018, an oil-based highly purified liquid formulation of CBD (Epidiolex) derived from Cannabis sativa was approved by the US Food and Drug Administration for the treatment of seizures associated with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS). The mechanisms underlying the antiseizure effects of CBD are unclear but may involve, among others, antagonism of G protein-coupled receptor 55 (GPR55), desensitization of transient receptor potential of vanilloid type 1 (TRPV1) channels, and inhibition of adenosine reuptake. CBD has complex and variable pharmacokinetics, with a prominent first-pass effect and a low oral bioavailability that increases fourfold when CBD is taken with a high-fat/high-calorie meal. In four randomized, double-blind, parallel-group, adjunctive-therapy trials, CBD given at doses of 10 and 20 mg/kg/day administered in two divided administrations was found to be superior to placebo in reducing the frequency of drop seizures in patients with LGS and convulsive seizures in patients with DS. Preliminary results from a recently completed controlled trial indicate that efficacy also extends to the treatment of seizures associated with the tuberous sclerosis complex. The most common adverse events that differentiated CBD from placebo in controlled trials included somnolence/sedation, decreased appetite, increases in transaminases, and diarrhea, behavioral changes, skin rashes, fatigue, and sleep disturbances. About one-half of the patients included in the DS and LGS trials were receiving concomitant therapy with clobazam, and in these patients a CBD-induced increase in serum levels of the active metabolite norclobazam may have contributed to improved seizure outcomes and to precipitation of some adverse effects, particularly somnolence.

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[WEB SITE] Cannabis Oil for Epilepsy – What You Need to Know

Cannabis Oil for Epilepsy – What You Need to KnowCredit: Pixabay

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[WEB SITE] Epilepsy Drug With Marijuana-Based Ingredient Could Be Available In The US This Year

 By Allan Adamson Tech Times

A new class of epilepsy drugs based on a marijuana ingredient could be become available in the United States as early as the second half of 2018 pending approval from the Food and Drug Administration.

Epidiolex

GW Pharmaceuticals, the maker of the drug called Epidiolex, announced on Wednesday the promising results of a clinical study of the drug.

A group of 171 individuals were randomly assigned to either receive Epidiolex treatment or placebo. The participants were between 2 and 55 years old with a condition called Lennox-Gastaut syndrome. They were also suffering from seizures existing drugs cannot efficiently control.

The participants on average had tried and discontinued use of six anti-seizure treatments and were experiencing 74 “drop” seizures per month. This particular seizure involves the entire body, head and trunk, and often leads to fall and other injuries.

LGS Patients Taking Epidiolex Sees Significant Reduction Seizures

Results of the study, which was reported in the journal Lancet,  showed that over a period of 14 weeks, 44 percent of the patients taking the drug saw significant reduction in seizures. The rate is significantly higher compared with the 22 percent in the placebo group. More of those who were given the experimental drug also experienced a 50 percent or greater reduction in drop seizures.

“LGS is one of the most difficult types of epilepsy to treat and the majority of patients do not have an adequate response to existing therapies,” said Elizabeth Thiele, from Harvard Medical School. “These results show that Epidiolex may provide clinically meaningful benefits for patients with LGS.”

Epidiolex is based on pure marijuana-derived cannabidiol or CBD. The cannabis compound has been known for its medical benefits sans making people feeling “stoned.”

Adverse Events Linked To Use Of Epidiolex

Adverse events associated with use of the drug include diarrhea, decreased appetite, sleepiness, vomiting, and fever. Once given the go-signal to be marketed in the United States, the drug is intended to be used as a prescription drug to be dispensed by doctors.

“Add-on cannabidiol is efficacious for the treatment of patients with drop seizures associated with Lennox-Gastaut syndrome and is generally well tolerated. The long-term efficacy and safety of cannabidiol is currently being assessed in the open-label extension of this trial,” investigators wrote in their report.

GW Pharmaceuticals has not yet disclosed the pricing of the drug, but Justin Gover, GW’s chief executive officer, said that the company is already in talks with health insurers about coverage.

via Epilepsy Drug With Marijuana-Based Ingredient Could Be Available In The US This Year : Health : Tech Times

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[WEB SITE] Cannabidiol Effective and Safe at 3 Months for Epilepsy – Medscape

PHILADELPHIA — New open-label data from the expanded-access treatment program involving the cannabidiol Epidiolex (GW Pharma) show the median reduction in frequency of convulsive seizures after 3 months of treatment was 45% in all patients but higher in those with Dravet syndrome, among the most severe types of epilepsy.

The data are “very positive and promising,” said lead author Orrin Devinsky, MD, professor, neurology, neurosurgery and psychiatry, and director, New York University Comprehensive Epilepsy Center.

A “big caveat,” however, is that this was an open-label study, he said. Results of the first of four placebo-controlled trials of this cannabidiol product are expected early next year.

Dr Devinsky reported the findings here during the American Epilepsy (AES) 69th Annual Meeting.

Convulsive Seizures

Epidiolex is a purified cannabidiol compound in an oil base that is administered as a liquid.

The efficacy analysis included 261 patients with continuous exposure to the drug and on whom investigators had evaluable data. These patients ranged in age from 4 months to 41 years with a median of 11.8 years.

In these patients, 19% had a known cause of their epilepsy. The most common diagnoses were Dravet syndrome (17%), Lennox-Gastaut syndrome (LGS), or another rare type of epilepsy (15%).

The median number of convulsive seizures per 28 days in these patients was 31, so this was a group of children and young adults with “very frequent seizures,” commented Dr Devinsky.

Patients started cannabidiol at a dose of 2 to 5 mg/kg per day, which was gradually increased to a maximum dose of 25 mg/kg per day. They were also taking an average of three antiepileptic drugs (AEDs).

The primary outcome was change in the number of convulsive seizures, which are relatively easy to count, said Dr Devinsky.

“The seizure had to last at least 3 to 5 seconds with convulsive activity, cause the child to drop or fall to the floor or have a tonic-clonic convulsive event,” he noted. These are readily identifiable by most parents who tracked these events in seizure diaries, he said.

The median convulsive seizure frequency reduction was 45.1% in all patients and 62.7% in patients with Dravet syndrome. The median reduction of atonic seizures was 71.1% in patients with LGS.

In terms of achieving a greater than 50% reduction in seizures, this rate was 47% among all patients. During the last 4 weeks of the trial (between weeks 9 and 12), 9% of all patients and 13% of patients with Dravet syndrome were seizure-free.

“These are numbers that are much greater than what I would have predicted, and certainly would have ever predicted for a placebo response,” said Dr Devinsky.

He stressed that the study population was “an extremely treatment-refractory group.” Such patients are at high risk for sudden unexpected death from epilepsy and status epilepticus.

Safety Data

Safety data were available on 313 treated patients. The most common adverse effects were somnolence (23%), diarrhea (23%), fatigue (17%), decreased appetite (17%), convulsion (17%), and vomiting (10%).

Dr Devinsky stressed that only 4% of all patients stopped the study medication because of adverse effects. “For an antiepileptic drug trial, that is relatively low.”

About 12% of patients withdrew because of lack of effectiveness, which “again was relatively small” in this type of trial, said Dr Devinsky.

Serious adverse events were reported in 34% of patients and included seven deaths. “None of these were felt by investigators to be related to the study medicine,” said Dr Devinsky.

Although these new results “add more fuel to the fire showing that this drug is likely to be effective for some people,” without a double-blind study “we are essentially blind to know what the truth is,” said Dr Devinsky.

An interesting study finding was that patients who were taking the AED clobazam had a better overall rate of treatment response (57% with a 50% or greater seizure reduction compared with 39%). This may reflect elevations in the desmethyl clobazam metabolite, he said.

“We think that some of the efficacy — and some of the toxicity — in some patients may have been related to the clobazam,” said Dr Devinsky.

He noted, however, that there was “absolutely no difference” in the response rate between patients with Dravet syndrome and LGS taking clobazam and those not taking that drug.

Asked whether increasing the dose of clobazam in patients already receiving this drug might have resulted in the same improved treatment response, Kelly Knupp, MD, Children’s Hospital, Aurora, Colorado, said that’s “possible.”

Increased clobazam levels probably reflect “some drug-to-drug interactions that need to be sorted out,” said Dr Knupp, who treats children with epilepsy.

She, too, is keen to know what the placebo effect is. “The value of doing a double-blind randomized study is that it takes into account that placebo effect; we just don’t really understand it here.”

In the meantime, she said she’s “guardedly hopeful” about the new results.

The study was funded by GW Pharma. Dr Devinsky reports receiving research support from GW Pharma.

Source: Cannabidiol Effective and Safe at 3 Months for Epilepsy

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