Acute myocarditis is an important cause of acute and fulminant heart failure in young adults and a leading cause of sudden cardiac death in people less than 35 years of age.
The most recent data from the ‘Highlights in General Cardiovascular Medicine: 2021’ suggests that the prevalence of myocarditis is approximately 16.2 per 100,000 population. In the United States, an orphan drug designation is granted for pharmaceuticals being developed to treat medical conditions affecting fewer than 200,000 people. These conditions are referred to as orphan diseases. The assignment of orphan status to a disease and to drugs developed to treat it is a matter of public policy in many countries and has yielded medical breakthroughs that might not otherwise have been achieved. In the U.S. and the European Union, orphan drugs are eligible for accelerated marketing approvals and companies developing orphan drugs typically receive other incentives, including a prolonged period of market exclusivity that can extend over seven years, during which the drug developer has sole rights to market the drug.
Acute myocarditis is characterized by inflammation in the heart muscle (myocardium). It has many causes, but the most common is a viral infection. In most patients the immune system is effective in clearing the virus in five to seven days, inflammation subsides, and the individual makes a full recovery. In a proportion of patients, however, the inflammation in the heart persists – perhaps as an auto-immune process – and causes decreased heart function with symptoms and signs of heart failure. In some cases, this becomes progressive and leads to a chronic dilated cardiomyopathy which is the most common reason for heart transplantation.
CardiolRx™, is an oral pharmaceutical that is currently being evaluated in a Phase II multi-national, double-blind, randomized, placebo-controlled clinical study, the ARCHER trial, to study the safety and tolerability of CardiolRx™, as well as its impact on myocardial recovery, in patients presenting with acute myocarditis. ARCHER has received regulatory clearance in multiple jurisdictions, including IND authorization from the FDA, and is expected to enroll 100 patients at major cardiac centers in North America, Europe, Latin America, and Israel. The primary endpoints of the trial, which will be evaluated after 12 weeks of double-blind therapy, consist of the following cardiac magnetic resonance imaging measures: left ventricular function (ejection fraction and longitudinal strain) and myocardial edema/fibrosis (extra-cellular volume), each of which has been shown to predict long-term prognosis of patients with acute myocarditis.
Since people with acute myocarditis have impaired heart function, treatment is based on standard-of-care recommendations for heart failure. This includes diuretics, ACE inhibitors, angiotensin receptors blockers, beta blockers, and aldosterone inhibitors. For those with a severe and sudden onset presentation, intensive care is often required, with the use of inotropic medications (to increase the force of the heart muscle contraction) and occasionally, heart-lung bypass or ventricular assist devices. There is otherwise no specific treatment for acute myocarditis although some patients have responded to immuno-suppressive therapy (azathioprine) in combination with steroids, but the data are not conclusive enough for this to be the recommended therapy.
Based on the large body of experimental evidence of the anti-inflammatory activity of cannabidiol in models of cardiovascular disease, Cardiol believes there is a significant opportunity to develop CardiolRx™ as a potential breakthrough therapy for acute myocarditis that would be eligible for designation as an orphan drug in the United States. CardiolRx™ is manufactured under cGMP, and the same concentration (100mg/mL CBD) as the first FDA-approved cannabidiol therapy for use as an orphan drug in rare forms of pediatric epilepsy.
An independent Clinical Steering Committee comprising nine highly distinguished thought leaders in cardiology from the Cleveland Clinic, the Mayo Clinic, the Houston Methodist DeBakey Heart and Vascular Center, the University of Ottawa Heart Institute, McGill University Health Centre, the University of Pittsburgh Medical Center, Tel Aviv Medical Center, and São Paulo University Medical School, has been established to design, oversee, and guide Cardiol’s Phase II multi-national ARCHER trial in acute myocarditis.