News|Articles|November 7, 2026

The HCM pipeline and Moving Past Beta-Blockers, with Ahmad Masri, MD, MS

Author(s)Ahmad Masri, MD, MS, Patrick Campbell

Ahmad Masri, MD, MS, highlights HCM agents to watch in 2027, including sotagliflozin and EDG-7500, and how MAPLE-HCM challenged beta-blocker use.

Beta-blockers have served as initial treatment for symptomatic obstructive hypertrophic cardiomyopathy (HCM) despite limited evidence of their efficacy.¹

The phase 3 MAPLE-HCM trial randomized 175 adults with symptomatic obstructive HCM to aficamten or metoprolol monotherapy, with results published in The New England Journal of Medicine.¹ At 24 weeks, peak oxygen uptake increased by 1.1 mL/kg/min with aficamten and declined by 1.2 mL/kg/min with metoprolol (difference, 2.3 mL/kg/min; 95% CI, 1.5-3.1; P < .001).¹

Patients receiving aficamten also showed greater improvements in New York Heart Association functional class, Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS), left ventricular outflow tract gradient, and N-terminal pro-B-type natriuretic peptide level.¹ Late-stage development in HCM now extends beyond cardiac myosin inhibition. Lexicon Pharmaceuticals completed enrollment in SONATA-HCM, a phase 3 trial of the dual SGLT1 and SGLT2 inhibitor sotagliflozin in nonobstructive and obstructive HCM, with topline results expected in the first quarter of 2027.²

The trial exceeded its target of 500 patients across more than 130 sites in 20 countries, and its primary end point is change in KCCQ-CSS at week 26.² Edgewise Therapeutics plans to start phase 3 development of EDG-7500, a cardiac sarcomere modulator designed to address impaired relaxation, in the fourth quarter of 2026.³ In the 12-week phase 2 CIRRUS-HCM trial, no patients receiving EDG-7500 had reductions in left ventricular ejection fraction to below 50%.³

Ahmad Masri, MD, MS, director of the Hypertrophic Cardiomyopathy Center and Cardiac Amyloidosis Program at Oregon Health & Science University, is a coauthor of MAPLE-HCM and principal investigator of ACACIA-HCM. Masri sat down with HCPLive at the American Heart Association Scientific Sessions 2026 in Chicago to discuss the HCM agents to watch in 2027 and how MAPLE-HCM reshaped the evidence base.

Q&A: Sotagliflozin, EDG-7500, and the HCM pipeline for 2027

HCPLive: Looking ahead to 2027, which studies, trials, or new agents should the field keep an eye on?

Ahmad Masri, MD, MS: It's such an exciting time to think about this, because again, everybody is realizing that there's severe unmet need and HCM is actually a sizable population that you can work with. The sites, the PIs, and the clinicians are now very sophisticated in how they find the patients and how they select them for studies, so part of the work has already been done there, which is really setting up for success. In terms of ongoing trials, we have a few. You have 2 new phase 3 trials that should come next year. One is with a sarcomere modulator called EDG-7500 that has a different mechanism of action than the CMIs, so that's going to be in a phase 3 trial. We have a phase 3 trial of a third CMI in class. I don't really like lumping these drugs together. Mavacamten, aficamten, and the third one, BHB-1893 or HRS-1893, all bind to different sites. They have different implications, so I like to treat them as individual drugs, if possible. That's another phase 3 that is also coming to sites.

Outside of this, there are actually a few other things that are quite novel in our thinking. One of them is very close to the finish line, which is a combined SGLT1 and SGLT2 inhibitor called sotagliflozin. The study is SONATA-HCM, and it should be reporting out next year. Keep your eye on that, because it's a completely different mechanism from what we usually do in HCM.

We have a new antifibrotic, and it's not just that it's a new antifibrotic that makes it very exciting. It is actually the first-in-human approach to addressing what's called a long noncoding RNA. It's an RNA medicine by HAYA Therapeutics called HTX-001 that is meant to reduce a certain long noncoding RNA called WISPER. If you downregulate it, you have less fibrosis. So it's hitting 2 things at the same time. One is characterizing this biology for all of medicine when you're addressing a long noncoding RNA, and the other is doing something in HCM that could extend to other disease spaces and hasn't been done, which is: How can you address the big problem of progression of fibrosis in diseases of the heart? We don't have solutions for that at this stage, so that's another mechanism we're very excited about.

There are a lot of things happening in the early clinical space. We also have a different mechanism of action on energy modulation. Ninerafaxstat is a drug that shifts how the heart uses energy, maybe allowing it to be smarter in how it works with a disease condition like HCM. We have a study called FORTITUDE-HCM that is in phase 2b and ongoing as well. So, lots of things happening.

HCPLive: How does your optimism about where the cardiomyopathy field is going now compare to where is was 5 years ago?

Ahmad Masri, MD, MS: In terms of optimism, we finally are at a stage where everyone understands the unmet need and understands the why. If you look back 6 or 7 years ago, there was actually hesitancy and suspicion: Why are you developing therapies in HCM? It's a solved problem. [UNCLEAR — please review: "and now you're inching it to"] I think we've already done that, which is convincing the majority that you need to step away from the traditional thinking and really become more evidence-based, and think about it like how we think in heart failure with reduced ejection fraction, for example. Show me the data and show me the evidence. I think MAPLE-HCM delivered big on this, where it challenged decades of beta blocker use in hypertrophic cardiomyopathy. It's a courageous trial. You could argue, why would you risk running such a trial? But it delivered for HCM what none of the other trials delivered, not because of efficacy, but because of showing that metoprolol, the primary drug used in all of the United States (outside, they use other beta blockers), is actually harmful to these patients. This is what I see changing: Finally, it is sticking that there is a problem here and that we have to move away from expert opinions and expert consensus. We have to actually think about the data and the evidence. Where do we have areas where we don't have data and evidence that we can actually work on and solve as well? I think there is no going back. The last 5 years have been amazing, and I think it's the start of something really great in hypertrophic cardiomyopathy and beyond, because this space now allowed us to think about cardiomyopathies as individual diseases, not as a group that is a subset of heart failure, which I think is really important.

Editor's Note: This transcript has been edited for grammar and clarity using artificial intelligence tools.