“We’re very excited for our patients about this addition to the toolbox for management of obstructive HCM. It won’t be for everyone — nothing ever is — but it is a very welcome tool,” says Sara Saberi, MD, a cardiologist and assistant professor of internal medicine at the University of Michigan Health Frankel Cardiovascular Center in Ann Arbor. Dr. Saberi was a coauthor on the EXPLORER-HCM study published in The Lancet, which was used as the basis for the drug’s approval. Manufactured by Bristol Meyers Squibb (BMS), Camzyos is the first and only FDA-approved drug that targets the underlying pathophysiology of obstructive HCM. Over time, the thickened walls become stiff, which reduces the amount of blood the heart is able to take in and pump out with each heartbeat. In obstructive HCM, the wall between the two bottom chambers of the heart also thickens, which can block or reduce blood flow from the left ventricle to the aorta. HOCM can cause sudden cardiac death in young people, including people who are in good physical condition. It can be difficult to diagnose — it’s often not identified until after a significant cardiac event. Current treatments for HOCM include beta-blockers, which are drugs that cause the heart to beat more slowly, as well as calcium channel blockers that lower blood pressure. Obstructive HCM stems from mutations to the gene that produces the heart muscle protein myosin; mavacamten is designed to block the excess myosin.
Who May Benefit From Taking Mavacamten?
The medication won’t be appropriate for everyone with HCM, says Saberi. “First of all, it’s only approved for use in those with symptomatic obstructive HCM with normal left ventricular systolic function, and not for people with nonobstructive HCM,” she says. In HOCM, symptoms can include shortness of breath, weakness, and exhaustion as a result of ordinary activities, such as climbing stairs or engaging in sports. For these patients, mavacamten offers a potential new therapy to improve symptoms, says Sitaramesh Emani, MD, cardiologist and director of heart failure clinical research at The Ohio State University Wexner Medical Center in Columbus. Dr. Emani was not involved in the clinical trials. In the clinical trial, many patients on mavacamten reported better exercise capacity and less shortness of breath when on therapy, says Emani. At the end of the study, 37 percent of participants treated with mavacamten improved on an endpoint measuring exercise capacity and symptoms, compared with 17 percent of participants in the placebo group. The medicine also delivered improvements in and quality of life versus placebo, according to the trials. “What is not known, however, is how mavacamten compares with surgical therapies that have been shown to improve HOCM patients’ symptoms and survival. In cases where surgical options may not be available or right for a patient, mavacamten may be an alternative,” says Emani. Saberi agrees that mavacamten will not replace surgery altogether. “Surgical myectomy will still be an important and necessary treatment for some patients with symptomatic obstructive HCM; mavacamten may replace the need for surgical myectomy in some.” The current FDA approval does not specify that patients need to fail “traditional” therapies to be prescribed the new drug; however, most patients in the clinical trial showing improvement (EXPLORER-HCM) were on treatments such as beta-blockers or calcium channel blockers before receiving mavacamten, says Emani. “I suspect many HOCM patients will continue to be prescribed these other traditional therapies first; those that continue to have symptoms will likely have mavacamten added,” he says.
Drug Comes With a Black Box Warning
Camyzos’s label carries a black box warning due to heart failure risk. A boxed warning on the label is FDA’s strictest warning and calls attention to serious or life-threatening risks of a drug. The mechanism of action of the drug makes it such that the squeeze function of the left ventricle should become mildly less vigorous, which is intended to bring the squeeze from super-normal into the normal range, explains Saberi. “But sometimes, it can do that too effectively and in a marked minority of trial patients, the left ventricular ejection fraction did become more significantly reduced, though that’s reversible,” she says. Because of that risk, the medication has to be monitored carefully and the primary way in which that will be done is with echocardiograms after initiating it and with any dose change of the medication, and then routinely while on a stable dose, says Saberi. According to the FDA, patients who have a serious intercurrent illness (such as a serious infection) or arrhythmia (atrial fibrillation or other uncontrolled fast heart rhythm abnormality) are at greater risk of developing impaired heart muscle contraction and heart failure with mavacamten. Patients must also avoid certain prescription and over-the-counter medicines that interfere with the metabolism (breakdown) of mavacamten. The monitoring described by Saberi isn’t optional — it’s part of the Camzyos Risk Evaluation and Mitigation Strategy (REMS), and prescriptions for the drug can only be written by providers who are enrolled in the REMS program. A Risk Evaluation and Mitigation Strategy (REMS) is a drug safety program that the FDA can require for certain medications with serious safety concerns to help ensure the benefits of the medication outweigh its risks. REMS are designed to reinforce medication use behaviors and actions that support the safe use of that medication. While all medications have labeling that informs healthcare stakeholders about medication risks, only a few medications require a REMS. “The risk of heart failure and worsening LV function (a measure of heart strength) is concerning. Thankfully, the percentage of patients who experienced this adverse event was low, and many of those that did have the adverse reaction recovered when the medication was discontinued,” says Emani. Because providers who prescribe will need to be a part of the REMS program, patients who receive mavacamten will likely be monitored well with adequate follow up, he says. “The risk profile and need to carefully monitor underscores the importance of HOCM patients to be evaluated at centers with expertise in treating HOCM, especially during the early use of this medication,” he says. It’s reported that the annual list price for Camzyos will be $89,500. The Institute for Clinical and Economic Review suggested a $12,000 to $15,000 yearly price would be cost effective for the benefit provided by the medicine.
