FDA REMS Program Shows Promising Results for Mavacamten in Hypertrophic Cardiomyopathy Treatment

In an interview with Pharmacy Times, Milind Desai, MD, MBA, cardiologist, vice chair of the Heart Vascular Thoracic Institute at Cleveland Clinic, shared results from the Risk Evaluation and Mitigation Strategy (REMS) program and its capabilities in reducing incidence of ejection fraction and heart failure.

Pharmacy Times: Can you introduce yourself? What did/will you present at the AHA 2024 Scientific Sessions?

Milind Desai, MD, MBA: My name is Melin Desai. I'm a cardiologist and the Vice Chair of Heart Vascular thoracic Institute at the Cleveland Clinic. I also direct our hypertrophic cardiomyopathy center at the Cleveland Clinic. Today, I'm going to be talking about the results of study that we are presenting at AHA 2024, which details the results of the 22-month real-world experience using mavamecten [Camzyos; Bristol-Myers Squibb Company] as part of the REMS program.

Pharmacy Times: What is the Risk Evaluation and Mitigation Strategy (REMS) Program?

Desai: The REMS program is something that is mandated by the FDA, especially in the context of a newer drug therapy. If the perception is that the benefits outweigh the risk in terms of informing the public beyond what they can put in a package insert. So, it is something that is mandated, which has 3 stakeholder: the patients, the physicians, as well as the pharmacies that that prescribe these medications.

Heart with stethoscope | Image Credit: © DARIKA - stock.adobe.com

Pharmacy Times: What were the most significant takeaways from the report results?

Desai: By way of background, mavamectan is an FDA approved therapy in the United States and multiple continents across the world for treatment of symptomatic, obstructive [HCM] patients. Now, mavamectan is a cardiac myosin inhibitor, which basically carries with it a small but important risk of left ventricular systolic dysfunction. So, the FDA mandated that this drug be approved under the REMS evaluation medication strategy program, and every patient within the United States who got prescribed mavamecten had to be part of the REMS program. And essentially, we are now reporting the results.

There were more than 6000 prescriptions for the REMS program for mavamectan and more than five 5500 patients got the first dispense, and the program was set up for ascertaining safety and efficacy. So basically, the questions that the FDA was interested in were, “what happened to the ejection fraction? How many patients dropped ejection fraction? How many patients developed heart failure that required hospitalization and the combination?” In addition, they also wanted to report efficacy in terms of outflow tract gradients, how many patients reached less than 30, how many patients reached less than 20, as per the package insert, and what were the doses at these things.

So bottom line is, what we found was, in these more than 5500 patients, the risk for the incidence of drop in ejection fraction was low, around 4.6% the risk for heart failure, hospitalization was even lower in the 1% range, and the risk of combination of less than ejection fraction 50% and heart failure require hospitalization was even lower, suggesting a, that the REMS program works.

The drug in the open market is relatively safe, as long as all the rules are followed. In fact, there were 29,000 patient status forms that were submitted. So, every time there is an interaction, a patient status form was submitted and the risk for ejection fraction drop was in. The overall patient status form was even much, much lower. So, so overall, from a safety perspective, it was deemed to be safe. About 70% patients had left ventricular track after a track gradient less than 30. So excellent response, and 75% patients were improved, or rather had these efficacy results on 5 and 10 mg [dose], or less than 10 mg. And very few patients required the highest amount of dose the. [These] results were replicated even in patients who took this drug for more than a year. So very similar results.

Pharmacy Times: Mavamecten is the only FDA approved treatment for class II-III obstructive hypertrophic cardiomyopathy (HCM). Are there any ongoing trials or recent research advancements in the treatment of HCM?

Desai: Right now we are blessed to be living in, what I would call, the Renaissance age for [HCM]. Lots of new stuff is happening, including multiple new drugs in development. There is another cardiac myosin inhibitor called aficamten (Cytokinetics) that has gone through one pivotal phase 3 trial, and that is, I believe, under consideration by the FDA for registration. So, we will hear about it in the next year or little longer, and it has a similar mechanism of action, so the results are very similar in terms of efficacy, et cetera.

There's another drug, a cardiac myosin modulator, a sarcomeric modulator, developed by another company. The molecule is EDG 7500 which is in earlier phase of development, and pivotal trials are coming. There are gene therapies that are emerging. There are all these drugs are also being tested in non-obstructive hypertrophic cardiomyopathy. So, lot and lots and lots of stuff is happening.

Pharmacy Times: What do you see coming down the pipeline for treatment of HCM?

Desai: I think the most important thing is we have come a long way from where most of the evidence in [HCM] was based on consensus opinions or retrospective observational studies. Now, we have a plethora of prospective research, so we should continue the momentum forward. I think the other big frontier is artificial intelligence and improving not only drug discovery, but improving our ability to appropriately diagnose these patients, so that the more we diagnose. The more we can address at the earlier on, we [can reduce] downstream advanced disease ramifications.