Any clinical trial program relies heavily on its administrators, advisors, and designers. Companies conducting significant research through clinical trials often rely on collaborators to carry out the programs or to oversee the efforts, and this is especially true when a smaller organization is involved. A company like Cardiol Therapeutics Inc. (Nasdaq: CRDL) (TSX: CRDL) is a prime example of this dynamic.
Cardiol is currently running two Phase II clinical trials of its proprietary CardiolRx™ therapy, an oral formulation for the treatment of both recurrent pericarditis and acute myocarditis. The list of the company’s advisors, administrators, designers, and collaborators is impressive as Cardiol seeks to advance a therapy for these rare but debilitating heart diseases.
The Locations
With the recent addition of Massachusetts General Hospital, or Mass General, Cardiol’s recurrent pericarditis trial is now utilizing eight prominent medical centers in the United States. The most recent U.S. News & World Report hospital rankings included three of them in their top 10 best hospitals for cardiology, heart and vascular surgery list. The Cleveland Clinic is first, the Mayo Clinic-Rochester is third, and Mass General is eighth.
In the U.S. News university rankings, Harvard University ranked first globally on the list of top schools for cardiac and cardiovascular systems. Mass General is Harvard’s teaching hospital, largely staffed by the best faculty Harvard Medical School has to offer.
“We are delighted to have the world-renowned Massachusetts General Hospital contributing to our MAvERIC-Pilot study enrollment,” commented Dr. Andrew Hamer, Cardiol Therapeutics ‘Chief Medical Officer and Head of Research & Development. “Mass General has been consistently ranked as a top hospital in the United States and has the largest hospital-based research program in the country. We look forward to the support of Mass General’s clinicians and participating patients towards reaching full enrollment in this ground-breaking study.”
While the MAvERIC-Pilot study focused on recurrent pericarditis is being conducted across the United States, Cardiol is reaching out across the world for its ARCHER trial focused on acute myocarditis. The trial has over 35 preeminent cardiovascular research centers currently enrolling patients across North America, France, Brazil, and Israel.
The People
The recurrent pericarditis trial was designed in collaboration with Dr. Allan Klein, MD, CM. He is the Director for the Diagnosis and Treatment of Pericardial Diseases, and Professor of Medicine, Heart, Vascular and Thoracic Institute at the Cleveland Clinic. He is one of the world’s leading experts on pericardial disease. In fact, he had a similar role in the trials for the only FDA-approved treatment for recurrent pericarditis – Kiniksa Pharmaceuticals’ (licensed from Regeneron Pharmaceuticals) ARCALYST®, the company’s commercial product name for rilonacept.
Other pericarditis Advisors among the six-member group include Dr. Allen Luis, MBBS, PhD. He is the Co-Director of the Pericardial Diseases Clinic at Mayo Clinic-Rochester. His area of focus is pericardial disease, and particularly recurrent pericarditis. Dr. Stephen Nicholls, MBBS, PhD leads Australia’s first dedicated heart hospital and integrated research institute and is President of the Cardiac Society of Australia and New Zealand.
On the acute myocarditis side, the ARCHER Steering Committee is comprised of ten noted specialists. Chairman of the committee is Dr. Dennis M. McNamara, MD, Director of the Center for Heart Failure Research at the University of Pittsburgh Medical Center and Professor of Medicine at the University of Pittsburgh. His research is centered around various aspects of cardiomyopathy (diseases of the heart muscle). Co-Chair Dr. Leslie T. Cooper, Jr., MD is the Chair of the Mayo Clinic Enterprise Department of Cardiovascular Medicine, as well as Chair of the Department of Cardiovascular Medicine at the Mayo Clinic in Florida. He is also a founder and former president of the Myocarditis Foundation.
Other members of the ARCHER committee hail from prestigious organizations including McGill University, Houston Methodist, the Cleveland Clinic, Charité Hospital at Freie Universität Berlin, Hospital das Clinicas of São Paulo University Medical School, Sorbonne University, and the Tel Aviv “Sourasky” Medical Center. Cardiol cast its net across the globe to find heart and myocardial experts capable of designing and implementing a world-class clinical trial.
The Science
The active ingredient in CardiolRx™, pharmaceutically manufactured cannabidiol, is known for its anti-inflammatory properties. Pericarditis is the inflammation of the sac surrounding the heart, and myocarditis is the inflammation of the heart muscle itself. In a general sense, anti-inflammatory medicines make sense. But the studies conducted by Cardiol that led to these trials are much more specific, and promising. For the purposes of this article, we will refrain from listing the various proteins and cytokines and leukocytes involved in the disease pathways of each disease. Instead we refer you to the excellent information presented by Cardiol for both the recurrent pericarditis study and the acute myocarditis study.
The active ingredient in CardiolRx™ has been shown to reduce the pro-inflammatory cytokines and inhibit the expression of the proteins responsible for their release. These effects have been confirmed in vitro and in models of various forms of myocarditis and pericarditis. Additionally, a Phase I trial demonstrated the safety, tolerability, and pharmacokinetics of CardiolRx™. No serious adverse events were reported from the trial, even at relatively high doses, and the company was able to use the findings to construct safe and potentially effective Phase II trials.
The Path Forward
Both recurrent pericarditis and acute myocarditis are conditions that qualify for the Orphan Drug designation, both in the United States (FDA) and in Europe (EMA). The programs encourage the research and development of therapies into diseases with smaller patient populations that are often overlooked by big pharma. Cardiol is planning to pursue the designation in both jurisdictions. The programs offer tax credits, fee waivers, specialized assistance from regulators, and access to grants for participating companies. After approval, orphan drugs can enjoy a seven to ten-year period of exclusivity without generic competition.
According to PharmaExec, over half of the US FDA’s drug approvals in 2021 were for orphan drugs. By 2026, orphan drugs are expected to constitute 20% of all prescription drug sales globally. Orphan drug sales are growing more than twice as fast as non-orphan drug sales. These trends point toward two things. One, pursuing the development of orphan drugs, in general, can be very lucrative. Two, big pharma has figured this out and has been acquiring smaller companies to add new revenue to their portfolios. Despite the current proliferation of orphan drug approvals, an estimated 7,000 rare diseases remain underserved. Plenty of headroom is still available for the orphan drug market.
With both the recurrent pericarditis study and the acute myocarditis trial recently passing 50% enrollment, now is an excellent time for investors to consider the potential value of these trials for Cardiol Therapeutics. With a market cap hovering around $67 million, this company has assembled a world-class team to conduct groundbreaking clinical trials for the treatment of two debilitating heart diseases. With Phase II results pending and planned Phase III trials down the road, the pathway is clear for value creation – stay tuned.
