FDA’s Findings on CBD Liver Damage 100% Debunked

Federal Drug Administration Findings on CBD and liver injury

What this report breaks down is the CBD clinical trails submitted to the FDA by GW Pharmaceuticals the makers of Epidiolex a Synthetic CBD based anti seizure medicine. After reviewing the so-called science and test studies submitted to the FDA there is without a doubt, that the FDA findings on CBD and liver damage is incorrect.

Summary:

Test subjects were administered over 20 times the amount of CBD than over the counter consumer CBD

For example, if a subject has a body weight of 100 lbs. (45 kgs) that subject was administered a dose of 900mgs a day of CBD, furthermore if a subject weighed 200 lbs. (91kgs) that subject was administered a dose of 1820mgs of CBD a day. Test subjects were giving these high dosages of CBD up to 90 days or more. This scenario of CBD intake for the average public CBD consumer does not happen, on average consumers take anywhere from 25mg’s to 40mg’s of CBD for a daily dose. Even if consumers wanted to use 900mg’s – 1800mg’s of CBD a day, realistically they couldn’t afford the price tag which would total over $5,000 a month.

Test subjects were already on medications during the study

All test subjects that had a rise in liver enzyme counts were already on a regimen of anti-seizure medications, mainly valproate, which on its own can cause serious liver injury.

The Report

Timothy Duggan (M.S.) 2/25/2020

Background

The information presented below is in response to the results published by the Federal Drug Administration (FDA), April 19, 2018, evaluating the use of Cannabidiol (CBD) oral solution (OS) for the treatment of seizures associated with Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS) in populations two years of age and older. This document is frequently cited as evidence of liver injury relative to the use of CBD-OS.
LGS and DS are rare epileptic syndromes with onset in early childhood. The syndromes are categorized as developmental and epileptic encephalopathies and is thought to contribute to developmental delay and behavioral abnormalities. Both syndromes are associated with higher rates of mortality in the general epileptic population. The onset of LGS is before the age of eight and peaking at the ages of three to five. DS is characterized by multiple seizure types and developmental arrest and regression. The onset is usually before the age of two. At this time, there are currently no medications for seizures in DS patients.

We challenge the assumption that the use of CBD-OS is associated with drug induced liver injury (DILI). The four studies cited below will demonstrate that markers for DILI were observed in subjects that were already on a regimen of anti-seizure medications, mainly valproate, which on its own can cause serious liver injury.

Summary of Controlled Studies

Study 1414
The endpoint was the percentage change from baseline to drop seizure. A drop seizure is an attack or spell involving the entire body, trunk and head. Patient caregivers record the number and type of seizures by utilizing the Interactive Voice Response System (IVRS). The IVRS is a telephone diary. Estimates of median differences between CBD-OS and placebo is approximately 95% confidence intervals (CI) calculated by using the Hodges-Lehman Approach. Results on the 225 patients showed a greater reduction in total seizure frequency (28-day avg). CBD-OS group was 38.6% vs placebo groups 18.5% and are considered vital with relevancy given to the CBD group.

Study 1423
This study was a 14-week randomized double-blind placebo-controlled trial on patients with LGS. It consisted of a 4-week baseline period and a 14-week treatment period (2-week titration plus 12-week maintenance). There were 171 patients and the results were seizure frequency reduction of 44.2% for CBD-OS and 23.5% for the placebo group.

Study1332 Parts A&B
This study evaluated DS patients where the endpoint was the percentage change from the baseline in total convulsive seizure frequency. The secondary endpoint was the total number of patients considered treatment responders. There were 61 patients treated with CBD-OS and 59 with a placebo. Total convulsive seizure frequency was decreased for those who were in the CBD-OS group. These studies were well controlled and considered accurate.

Hepatic Adverse Events

A detailed evaluation of liver safety signal was conducted on all four studies by the Division of Gastroenterology and Inborn Errors Products (DGIEP) and the office of Surveillance and Epidemiology (OSE). Results were confirmed by the FDA review team. The principal safety data was generated in 2 trials involving DS study 1332 parts A&B, and two trials from LGS studies 1414 and 1423. The data from these four double blind placebo-controlled studies constitute the database and serve as the primary basis for comparisons and frequencies of adverse events.

There were no events of liver failure or death due to liver injury. The liver injury associated with CBD-OS (elevation of liver enzymes) appears to be relatively mild and reversible on drug discontinuation. It is dose-related with a much higher incidence on the 20 mg/kg/day dose. For example, if a subject has a body weight of 100 lbs. (45 kgs) that subject was administered a dose of 900mg’s a day of CBD, furthermore if the subject weighed 200 lbs. that subject was given (91kgs) that subject was administered a dose of 1820mg’s of CBD a day. This scenario of CBD intake for the average public CBD consumer does not happen, on average consumers take anywhere from 25mg’s to 40mg’s of CBD for a daily dose.

Elevation of liver enzymes is noted most frequently in the first 30-90 days of treatment and is rare after 200 days of treatment. Concomitant Valproate is identified as the most common risk factor for the increase in liver injury markers. Risks associated with CBD-OS appeared to be acceptable per the FDA.

Outcome

At the time of the original New Drug Approval (NDA) submission, 1756 subjects were exposed to CBD-OS. One fourth of the group were exposed in placebo-controlled trials for DS studies 1332 parts A & B and LGS studies 1414 and 1423. CBD-OS was granted orphan status for the treatment of both DS and LGS. Given the prevalence of these diseases, the FDA finds the exposure adequate to support a reasonable assessment of safety. Clinically meaningful statistically significant reductions in seizure frequency were demonstrated in three adequate and well controlled trials in LGS and DS, which are considered serious life-threatening illnesses. The risk benefit profile established by the data in the application appears to support approval associated with DS and LGS treatment.
The FDA and the Center for Drug Evaluation & Research (CDER) plan to investigate the efficacy and safety data from clinical trials in DS and LGS treatment. At this time, they support the approval of CBD-OS for the treatment of seizures associated with DS and LGS.

CBD-OS is a first-in-class antiepileptic drug product sponsored by GW Research, Ltd., a subsidiary GW Pharmaceuticals that operates under Greenwich Biosciences, Inc. in the United States. They hold the Investigational New Drug (IND) application for CBD-OS as an oral adjunct treatment of two epilepsy conditions in children who remain on their current antiepileptic medication. CBD-OS was granted orphan drug designation and rare pediatric designation for treatment of DS and LGS as well as fast track designation.

Based on the data presented, the sponsor has concluded that there is an adequate margin of safety for the usage of CBD-OS in the treatment of pediatric DS and LGS.

Source Link to clinical trail – Efficacy and Safety of GWP42003-P for Seizures Associated With Lennox-Gastaut Syndrome in Children and Adults (GWPCARE3)

 

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