The evolution of cannabis as a legitimate and proven medicine continues with yesterday’s announcement that America’s first cannabis-based drug had been approved by the US Food and Drug Administration (FDA).
Epidiolex is the first FDA-approved drug that contains a purified drug substance derived from cannabis. Importantly, it is also the first time the FDA has approved a drug specifically for the treatment of patients with Dravet syndrome.
Epidiolex was developed by GW Pharmaceuticals and its US subsidiary Greenwich Biosciences. GW is currently one of the world’s largest pharmaceutical developers with a market capitalisation of approximately US$4.2 billion (A$5.67 billion).
However, the approved drug is a synthetic compound that mixes both natural and artificial ingredients which can cause severe side-effects with the FDA unwilling to sanction the use of “unapproved products, with uncertain dosages and formulations” – referring to home-grown entirely natural cannabis plants and cannabidiol-based products being produced in places where cannabis has been legalised or decriminalised.
The US regulator insists that only its approved pharmaceutical compounds are suitable for patients and that naturally-grown cannabis plants containing both tetrahydrocannabinol (THC) and cannabidiol (CBD) are not recommended.
According to the FDA, it is “prepared to take action when we see the illegal marketing of CBD-containing products with serious, unproven medical claims.”
Despite the breakthrough for medical cannabis and its two active ingredients – CBD and THC – CBD is still considered as a Schedule 1 substance in the US under the purview of the Controlled Substances Act because it comes from the cannabis plant.
According to the Drug Enforcement Administration (DEA), schedule 1 drugs are substances or chemicals defined as “drugs with no currently accepted medical use and a high potential for abuse,” a classification that includes drugs such as heroin, LSD and ecstasy.
This innate contradiction between the FDA and the DEA is expected to be resolved if or when CBD is reclassified, but until then, the substance remains a controlled substance that’s banned by the US authorities.
The FDA approved Epidiolex, a chemical opioid that treats epileptic seizures and has been proven to be highly effective for two rare and severe forms of epilepsy known as Lennox-Gastaut Syndrome and Dravet Syndrome.
Epidiolex’s effectiveness was studied in three randomized, double-blind, placebo-controlled clinical trials involving 516 patients suffering from severe epilepsy. Epidiolex was shown to be effective in reducing the frequency of seizures when compared with a placebo.
However, despite the FDA approval and a successful negotiation of clinical trials, Epidolex’s chemical and artificial foundations generated side-effects as opposed to natural medicines which are far more suitable for human consumption and that do not cause severe side-effects.
According to the FDA, the most common side-effects experienced by Epidiolex-treated patients during the clinical trials were: sleepiness, sedation and lethargy; elevated liver enzymes; decreased appetite; diarrhoea; rash; fatigue, malaise and weakness; insomnia, sleep disorder and poor-quality sleep; and infections.
Epidiolex also caused either mild or severe liver injury, induced nausea, vomiting, abdominal pain, fatigue, anorexia, jaundice and dark urine.
The FDA also said that “as is true for all drugs that treat epilepsy, the most serious risks include thoughts about suicide, attempts to commit suicide, feelings of agitation, depression, aggression and panic attacks.”
The FDA’s statement echoes previous cases where suicidal tendencies and mental disorders were reportedly being caused by popular drugs such as Accutane and Roacutane, prescribed to treat acne in adolescents. Roacutane was withdrawn from US pharmacies in 2013 following multiple successful lawsuits.
Lennox-Gastaut Syndrome and Dravet Syndrome are similar conditions and are considered as brain dysfunctions that affect around 1 in 20,000 people.
At the current time, there is conflicting research into the conditions – some researchers suggest they are caused by “non-hereditary genetic mutations” while others claim that epilepsy is caused by environmental factors such as diet, living conditions and general quality of life.
Both conditions are typically discovered in the first year of life in previously healthy children, with hereditary causes ruled out.
This has led to criticism that environmental factors including poor diet and strong chemicals sustained by mothers during pregnancy, or by the child in the first year since birth, are the primary cause of epilepsy.
Critics have also pointed to widespread vaccination programs as a causal factor, but this has been staunchly denied by the pharmaceutical industry and government-sponsored healthcare institutions.
“This approval serves as a reminder that advancing sound development programs that properly evaluate active ingredients contained in marijuana can lead to important medical therapies,” said FDA Commissioner Scott Gottlieb.
Australian knock-on effect
Yesterday’s FDA approval is an important milestone and a firm precedent for future drug development. The stage is now set for biopharmaceutical development to make further inroads into the capabilities of cannabis and its reported health effects.
One of the many Australian biotech companies already setting the pace for developing medicines based on medical cannabis include the likes of Botanix Pharmaceuticals (ASX: BOT), a medical dermatology company that is currently developing a range of CBD-based solutions within the dermatology niche i.e. creams, salves and oils that are applied to the surface of the skin.
Botanix is currently developing BTX 1503 as a new treatment for moderate to severe acne. The basis of its methodology is to use synthetic cannabidiol to target multiple pathologies involved in the development of acne utilising Botanix’s proprietary Permetrex drug delivery technology.
Last month, Botanix got the all-clear from FDA for a phase 2 clinical trial into BTX 1503, a synthetic product that treats acne and will also conduct a clinical trial of BTX 1204, a product to treat atopic dermatitis and eczema.
“The approval of Epidiolex is an important validation of the therapeutic potential of cannabidiol and the FDA’s preference for high-quality drug and consistent delivery,” said Matt Callahan, founder and executive director of Botanix Pharmaceuticals.
Mr Callahan added that “we believe our approach to drug product manufacturing using pure synthetic cannabidiol, combined with the Permetrex delivery system addresses these specific FDA concerns.”
Botanix’s Phase 2 acne clinical trial is a 12-week study to evaluate the safety and efficacy of BTX 1503 in patients with moderate to severe acne and will enrol approximately 360 patients across 5 dose groups, involving leading dermatology clinics across the US and Australia.
Botanix says its study will “commence shortly” and is expected to take approximately 12 months to complete. Its atopic dermatitis clinical trial is planned to commence in the third quarter of this year and could also take up to 12 months to complete.