Recurrent pericarditis (RP) is a debilitating disease in need of better forms of treatment. Often misdiagnosed, the flare-ups of the condition can plague patients for years, leaving them unable to conduct their normal lives from the pain and physical limitations placed on them while incurring frequent visits to doctors, emergency rooms, and even hospital stays. There is only one FDA-approved therapy for RP, an injectable IL-1 blocker called Arcalyst® from Kiniksa Pharmaceuticals (Nasdaq: KNSA) that has been on the market for about five years now. Arcalyst® has been a game-changer in the RP world, given its effectiveness and steroid-sparing potential. It is very good at reducing recurrence risk, but it is very expensive (~$300K USD per year), requires weekly injections, and comes with its own challenges and limitations including immunosuppression risk, dependence, and high relapse rate following discontinuation, suggesting it suppresses the disease but does not modify it.
Cardiol Therapeutics (Nasdaq: CRDL) (TSX: CRDL) is now developing CardiolRx™, an oral drug with a very clean safety profile, as another option for RP patients. Cardiol is in the midst of a pivotal Phase III trial underway at many of the top cardiac health centers across the United States, with results expected in the early part of 2027. If the trial demonstrates efficacy and the safety and tolerability is reinforced, the company expects to file a New Drug Application with the U.S. FDA to make CardiolRx™ the second approved treatment for RP.
Paul Cremer, MD, MS is a Principal Investigator for Cardiol’s Phase III MAVERIC trial. An expert in cardiac imaging and auto-inflammatory cardiovascular disease, Dr. Cremer is deep into the world of pericardial disease through his imaging background, his time at the Cleveland Clinic, and his current position as Associate Director of the Northwestern Medicine Bluhm Cardiovascular Institute in Chicago. Bluhm is one of only 15 care sites approved by the American Heart Association’s Addressing Recurrent Pericarditis Initiative.
Dr. Cremer recently sat down with biotechnology analysts from Canaccord Genuity to discuss CardiolRx™, the MAVERIC trial, the current state of affairs in the RP therapy world, and the potential role for Cardiol’s drug candidate. You can view the whole discussion here.
Readers take note: some of the material presented here is forward-looking and illustrative. There is no guarantee that the MAVERIC trial will succeed, or that the FDA will approve CardiolRx™.
The Starting Point
The MAVERIC trial is designed to test whether an oral investigational therapy can help maintain freedom from recurrence in an enriched population at high risk to recur. Seventy-five percent (75%) of patients experience a flare-up of RP within the first 12 weeks after withdrawing from an IL-1-blocker. The trial seeks to determine whether CardiolRx™ can prevent those recurrences for a period of 24 weeks following cessation of the IL-1 blocker therapy. That outcome alone would be a godsend for multi-year RP patients that have exhausted their treatment options. Tell any patient that has been injecting expensive weekly IL-1 blockers that there is an oral treatment which is less expensive, more tolerable, and which may reduce or even eliminate recurrences and they would likely jump at the chance.
The potential impact of a positive outcome for CardiolRx™ in MAVERIC is expected to extend to the majority of the 40,000 patients in the United States with recurrent pericarditis.
Earlier Interventions Possible
Before RP patients start using IL-1 blockers they are generally treated with NSAIDs like ibuprofen in combination with colchicine. Many cases of pericarditis are resolved after the initial diagnosis with this one-two punch, and the NSAID/colchicine regimen is used to help control symptoms of recurring episodes for those cases that aren’t resolved the first time around.
But long-term NSAID use is not recommended and comes with a host of side effects like gastrointestinal issues, kidney problems, and increased risk of cardiovascular complications. Colchicine is a powerful anti-inflammatory drug typically used to treat gout and high risk coronary artery disease. Common side effects include nausea, diarrhea, and vomiting. Extended use needs to be closely supervised by medical professionals and can decrease the body’s immune response.
As Dr. Cremer discusses in the interview, what he would really like to see on the market is a more effective and better tolerated drug that could replace colchicine. Cardiol’s Phase II results point to that possibility, as subjects experienced marked, rapid, and durable reductions in pericarditis pain and inflammation, and a substantial reduction in the number of pericarditis recurrences per year. Importantly, the trial monitored patients for 18 weeks after the treatment period, well beyond the typical 8-12 week window for recurrences. Should the Phase III MAVERIC trial show similar efficacy, CardiolRx™ could potentially serve as a colchicine alternative. Importantly, Dr. Cremer highlights that the actions of both colchicine and CardiolRx™ occur upstream and prior to the actions of IL-1 blockers, meaning that, like colchicine, it would make sense to utilize Cardiol’s potential new drug prior to the IL-1 blockers.
If RP patients don’t respond to the NSAID/colchicine combo, or if they don’t tolerate the treatment, another course of action is required. For many years that course was the prescription of corticosteroids, which come with their own consequences. Short-term use commonly causes increased appetite, weight gain, fluid retention, high blood sugar, insomnia, and mood swings. Long-term use can lead to bone thinning (osteoporosis), high blood pressure, weakened immunity, and skin changes. Here is another step in the treatment of progressively worse RP cases where CardiolRx™ could be used as an alternative.
Steroids are sometimes being replaced as the second line treatment by IL-1 blockers, especially in clinics with extensive pericardial disease experience. We’ve covered the various issues with IL-1, and Cardiol’s Phase III trial is studying whether CardiolRx™ can be used to limit recurrences after prolonged use of the drugs. Dr. Cremer thinks both doctors and patients would be very interested in a safe, well-tolerated, less expensive oral treatment like CardiolRx™ even if it gave patients only a 40-50% chance of decreasing or eliminating flare-ups.
The Takeaway
Doctors who treat RP patients are looking for more options that can help the estimated 40,000 Americans who seek treatment for the disease annually, including approximately 20,000 new cases each year. Yet there is no perfect solution for this condition. Nobody is predicting CardiolRx™ will be the cure, but there is a distinct possibility of the drug providing a safe and effective alternative at multiple points along the treatment paradigm. Once again, there is no guarantee the MAVERIC Phase III trial will succeed, or that the FDA will approve the drug. The need is there, the signs from the Phase II are positive, and the results are expected earlier rather than later next year. It’s a good time to have Cardiol Therapeutics on your radar, whether you’re a patient, a health care professional, or an investor.
Author’s Disclosure: This article reflects the author’s independent analysis and personal views. The content is provided for informational purposes only and should not be considered financial or investment advice. Readers are encouraged to conduct their own independent research and due diligence before making any investment decisions.
