Martin Maron, MD, medical director of the Hypertrophic Cardiomyopathy Center at Lahey Hospital and Medical Center, participates in a Q&A related to the approval of mavacamten for symptomatic obstructive hypertrophic cardiomyopathy.
With approval on April 28, mavacamten (Camzyos) represents a welcome addition to the armamentarium of specialists treating patients with obstructive hypertrophic cardiomyopathy.
Based on data from the pivotal EXPLORER-HCM trial, the FDA granted approval to the first-in-class, oral, allosteric modulator of cardiac myosin for improving functional capacity and symptoms in patients with symptomatic New York Heart Association (NYHA) class 2-3 obstructive hypertrophic cardiomyopathy.
“This is a first-in-class medicine specifically for patients living with symptomatic obstructive HCM,” said Milind Desai, MD, MBA, director of the Hypertrophic Cardiomyopathy Center and director of clinical operations in Cleveland Clinic’s Heart Vascular & Thoracic Institute, in Bristol Myers Squibb’s press release announcing the approval. "With this FDA approval, U.S. cardiologists now have a new pharmacological option for eligible patients that targets the underlying pathophysiology of the disease.”
With an interest in learning more about the reaction to the approval and how EXPLORER-HCM data might inform use in real-world settings, Practical Cardiology™ reached out to Martin Maron, MD, medical director of the Hypertrophic Cardiomyopathy Center at Lahey Hospital and Medical Center, and that conversation can be found below.
Practical Cardiology: What is your reaction to the approval?
Maron: I wasn't surprised about the approval. I thought, based on the prior evidence, from EXPLORER-HCM and VALOR that there was going to be regulatory approval of the drug. The question, perhaps more than that, was: What were the restrictions going to be around the use of the drug?
PC: You mentioned restrictions. In their release, Bristol Myers Squibb noted the creation of a Camzyos REMS Program. How does this impact the way that you might be able to prescribe this drug or use it in clinical practice?
Maron: For necessary reasons, it is a pretty restrictive and challenging with the REMS program that surrounds the use of the drug. The REMS program means that, because of safety concerns related to the drug that we're seeing in some of the prior studies, the regulatory agency has created a program, that acts like a safety net, to, hopefully, mitigate or decrease some of these safety concerns.
The biggest concern associated with this drug is heart failure from systolic dysfunction, meaning the heart pump function decreases too much in an individual patient. So, this REMS program that's been put together is about mitigating that by ensuring that monitoring of heart function is done at pretty close intervals after the initiation of the drug and well beyond initiation of the drug—it appears that it's almost indefinite monitoring, but much more frequent when the drug begins. Nevertheless, there are a lot of echocardiograms and ultrasounds of the heart that are necessary and mandated around the use of this drug that will make, to some degree, the drug less appealing because it will make it much more complicated for some patients to be able to meet those requirements in a way.
PC: How do you balance the increased risk of heart failure, which is noted in a Boxed Warning within the full prescribing information for mavacamten, something that is going to prevent a large number of patients from receiving this drug?
Maron: I think the answer is complicated because I think it involves a number of different things—some of which have not yet really been resolved yet. The true impact on heart failure from systolic dysfunction is really hard to judge because the information about it is coming from small studies that haven't really followed patients for that long. So, their real-world experience with the drug could be different than what's happened in clinical trials.
So, we don't really know the magnitude of that particular issue, which is a very important one. It's hard to know, for that reason, exactly what the impact of that would be on patients' desires to go on the drug or on cardiologists' enthusiasm and recommending of the drug. It's hard to judge that right now. I think it's obviously a real concern.
It also has to be balanced against the fact that in this disease, there are alternative treatment options that patients could pursue if they were concerned about that safety issue. There are other drugs and there are invasive procedures that can make patients feel better. So, it's not as if this is the only option available for this problem.
So, that's, that's kind of where we are on that. I think we'll know more with time and that's really the essence here: We're going to need more time to really understand where this drug fits in and exactly where our comfort level with it is as we go forward.
PC: What do you foresee as the biggest implementation challenges?
Maron: I think it's going to be the heart failure risk and it's going to be cost. Cost is going to be another really important factor here. Although we should soon learn the cost of the drug, the estimates that have been provided that seem to be probably in the ballpark of what the cost will be and suggest it's going to be a pretty expensive drug. So, that could, in itself, be the biggest challenge because of how different insurers may view that and may make access for patients more complicated and limited as well. So, that's the other challenge.
PC: Any other thoughts surrounding the approval?
Maron: I think it's exciting that we have another potential drug option for symptomatic obstructive HCM. I think we're all enthusiastic about that. Now that we've got regulatory approval, I think we also have to recognize, too, that there are also very good treatments that currently exist and are very beneficial for patients too. So, I think as we move forward we have to be balanced to some degree in how we integrate the drug into the current algorithm with treatment options. I think we need to be open to really looking forward to understanding more about the drug with time and experience. I think that's going to be really important here given that we've had a limited experience so far.
Editor's Note: This transcript has been edited for length and clarity.