Home Alernative Pharma Orphan Drug Designation is Proven Path for CBD

Orphan Drug Designation is Proven Path for CBD


The only cannabidiol (CBD) drug approved by the U.S. Food and Drug Administration (FDA) to date is Epidiolex®. Developed by GW Pharmaceuticals, Epidiolex is approved for the treatment of two rare forms of epilepsy—rare enough to meet the FDA guidelines for orphan disease designation because they affect less than 200,000 people in the U.S. In some ways, GW Pharma’s success is a roadmap for capitalizing on the potential therapeutic benefits of CBD in these early days of cannabis drug development.

Here, we will discuss how the success of the orphan designation informs Cardiol Therapeutics Inc.’s (TSX: CRDL) (OTCQX: CRTPF) effort to develop CBD as a treatment for acute myocarditis. The Canadian-based company is utilizing pharmaceutical CBD in its research programs focused on various forms of heart failure and is preparing to launch its own brand of pharmaceutical CBD into the Canadian medical cannabis market.

Acute Myocarditis as Orphan Disease

To qualify for the FDA’s orphan drug designation, the target disease has to affect less than 200,000 Americans. The orphan drug program was established by the FDA to incentivize companies to develop therapies for rare diseases that might otherwise be overlooked. It has worked. Since the passing of the Orphan Drug Act in 1983, over 600 drugs have been developed for diseases that meet its criteria, an average of about 150 per decade. In the ten years prior to the introduction of this program , fewer than ten such drugs came to market.

(1): Lennox-Gastaut Syndrome

(2): Dravet Syndrome

Source: Cardiol Therapeutics Presentation

Acute myocarditis is the leading cause of sudden cardiac death among people younger than 35 years of age. It is thought to affect around 22 out of every 100,000 people, equating to approximately 73,000 Americans. It is characterized by excessive inflammation of heart tissue, most often following a viral infection, and is believed to be the result of an immune response to the infection. This process results in increased apoptosis (death) of cardiac cells and an impairment to cardiac function. Some such patients develop profound heart failure and require circulatory support. There is no specific treatment for acute myocarditis, with cardiologists falling back on standard heart failure drugs like diuretics, ACE inhibitors, and beta blockers that offer limited effectiveness. In advanced cases, clinicians may utilize powerful steroids, which have significant toxicity, in an effort to reduce the inflammation.

Of emerging medical interest is the fact that a high percentage of patients who are hospitalized with COVID-19 are developing cardiovascular complications, and some of these may be the result of myocardial infection by the virus. Scientists in Germany studied 100 recovered patients between the ages of 45 and 53 with severity of illness ranging from asymptomatic to mild symptoms. MRI scans revealed 78% of them had some sort of cardiac involvement, with 60% experiencing ongoing inflammation of the heart, most commonly characterized as myocarditis. It’s a small sample, and the researchers concluded that “These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19.” Anecdotally, Eduardo Rodriguez, a 27-year-old pitcher for the Boston Red Sox, recently revealed he has myocarditis as a result of his COVID-19 illness.

Additionally, COVID-19 patients with pre-existing heart disease are more likely to be hospitalized and have significantly worse outcomes, including death, than those without heart disease. On top of its planned clinical study in myocarditis patients, Cardiol is also exploring the potential of developing its pharmaceutical CBD as a cardioprotective treatment in COVID-19 patients with a prior history of cardiovascular disease. The company recently filed a patent application in the United States covering the use of its CBD formulation in the treatment of COVID-19.

CBD as an Anti-Inflammatory

Developing a therapeutic strategy that reduces inflammation without causing serious adverse side effects is key to improving treatment options for myocarditis patients. Data accepted for presentation at the virtual sessions of the American Cardiology Sessions in March 2020, demonstrating that Cardiol’s CBD formulation significantly reduced inflammation and fibrosis in a model of inflammatory heart failure, suggest Cardiol is on the right track. Research in the published literature also shows that “CBD reduces the levels of pro-inflammatory cytokines, inhibits T cell proliferation, and reduces migration and adhesion of immune cells that lead to excessive inflammation.” These are just the types of therapeutic responses that would be expected to offer significant benefit to patients with myocarditis and other forms of heart failure.

Pharmaceutical CBD Avoids Botanical Drug Concerns

The FDA very recently released a draft document offering guidance for and thoughts on the development and approval process for cannabis-derived drugs. To be clear, the document is a work in progress, not a final policy; but it does offer insight into the concerns surrounding cannabis-derived products and drug development. It is not surprising that quality control and consistency are major themes. Companies pursuing cannabis-based research need to fully characterize all compounds in the product, including but not limited to cannabinoids, terpenes, and flavonoids. Batch-to-batch consistency must be documented and assured, testing for the presence of pesticides is required, and microorganisms must be detected. These concerns are not unique to cannabis but are common for the development of botanically sourced compounds.

What is unique for cannabis is the apprehension over its psychoactive properties brought on by the presence of tetrahydrocannabinol (THC).

Cardiol Therapeutics has developed pharmaceutical CBD in conjunction with its exclusive pharmaceutical partner Dalton Pharma Services. Dalton and Cardiol have a combined 15 years’ experience in the research, development, and manufacture of pharmaceutical cannabinoids.  Unlike many CBD products, Cardiol’s CBD formulations are produced in a cGMP and FDA-registered facility. Aspirin was discovered in the bark of the willow tree and later manufactured in labs to achieve scale, purity, and consistency; similarly, Cardiol’s pharmaceutical CBD formulations are manufactured in a controlled laboratory environment. Producing CBD formulations in this way removes many of the concerns listed by the FDA regarding consistency, purity, and stability of cannabis-derived medicines. Cardiol’s pharmaceutical CBD is essentially THC free (<5 parts per million), alleviating any potential psychoactive effects.

The Upshot

Cardiol Therapeutics is pursuing the development of its CBD formulations to initially address an orphan disease, the accelerated regulatory approval path that has proven successful for GW Pharma. For GW Pharma, success in developing its CBD formulation, Epidiolex, through to FDA approval resulted in the creation of over $5 billion in shareholder value between 2014 and 2018. The fact that Cardiol is developing its CBD formulation for an orphan disease indication (acute myocarditis) with an addressable market almost twice the size of GW Pharma’s, serves to illustrate the value creation potential of Cardiol Therapeutics.

Acute myocarditis affects roughly twice as many patients as do the rare forms of epilepsy treated by Epidiolex, and, importantly, Cardiol has other lines in the water with the pending launch of its commercial CBD product and its research program into CBD as a treatment for heart failure. Chronic heart failure is a far more prevalent condition than myocarditis, affecting over six million people in North America, with associated healthcare costs exceeding $30 billion annually in the U.S. alone.

Cardiol is well funded, having recently closed a round of $17.25 million. The company also recently brought on board CNBC analyst and Wall Street veteran Steven Grasso to raise its profile in the U.S. investment community. Cardiol Therapeutics is charging forward, and investors should take note of this growing company.


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