In a new trial, an experimental drug helped patients with an inherited heart muscle condition feel better and exercise more.
Two new studies found that aficamten improved exercise capacity and reported health in people with nonobstructive hypertrophic cardiomyopathy (nHCM). This inherited condition thickens and stiffens the heart muscle, often causing shortness of breath and limiting physical activity.
Aficamten reduces the activity of cardiac myosin, a protein that helps the heart muscle contract. The studies, published in The New England Journal of Medicine and Circulation, tested whether easing those contractions could benefit patients with nHCM, who account for about 30 percent of people with hypertrophic cardiomyopathy.
Patients Felt Better and Exercised More
In the trial reported in The New England Journal of Medicine, 517 participants received aficamten or a placebo. After 36 weeks, the aficamten group showed greater improvements in both reported health status and peak oxygen consumption, a measure of how much oxygen the body can use during intense exercise.
Patients with nHCM have lacked a treatment targeted to the condition, said Lubna Choudhury, MD, a professor of Medicine in the Division of Cardiology and a co-author of both studies. “With these new studies, I can now recommend to patients a specific designer drug therapy which can work for them, make them feel better, and also improve their overall heart failure status.”
The measured gain in exercise capacity helped show that the benefit extended beyond how patients described their symptoms. “This was a game changer, because that really shows we can impact these patients, not only in the way they feel, but objectively in the cardiac function that we’re measuring with the peak VO2,” Choudhury said.
Heart Scans Offer A Possible Explanation
The companion Circulation study analyzed heart ultrasound scans taken throughout the trial. Compared with placebo, aficamten reduced signs of excessive contraction and improved several measures of diastolic function, the heart’s ability to relax and fill with blood between beats.
Researchers also found improved tissue Doppler measurements of how the heart muscle relaxes, changes in blood volume within the left ventricle, and lower markers of cardiac stress. These findings raise the possibility that aficamten affects the underlying disease process as well as relieves symptoms, though longer follow-up is needed to determine whether the changes last.
“We saw indications from the Circulation paper that diastolic dysfunction parameters improve. That may explain why the patients feel better,” Choudhury said.
Longer Follow-Up Will Test The Benefits
The trial built on earlier evidence that aficamten helps people with obstructive HCM. Researchers wanted to learn whether those benefits would extend to patients without an outflow tract obstruction, who have historically had no targeted treatment options.
The benefits also came with a reason for careful monitoring. In the nHCM trial, a reversible decline in a measure of the heart’s pumping ability occurred more often with aficamten than with the placebo.
An ongoing extension study is following people with both forms of HCM to assess aficamten’s effects over a longer period. “We want to get more long-term data on how these things look after several years in these patients,” Choudhury said.
References:
“Aficamten for Symptomatic Nonobstructive Hypertrophic Cardiomyopathy” by Ahmad Masri, Martin S. Maron, Ankit Bhatia, Maria Luisa Peña-Peña, Mark V. Sherrid, Estevao Lanna Figueiredo, Michael Arad, Roberto Barriales-Villa, Lubna Choudhury, Brian L. Claggett, Caroline J. Coats, Edileide de Barros Correia, Juan Pablo Costabel, Perry M. Elliott, Jorge E. Silva Enciso, Pablo Garcia-Pavia, Junbo Ge, Sheila M. Hegde, Gregory D. Lewis, Renato D. Lopes, Matthew W. Martinez, Mathew S. Maurer, Zi Michael Miao, Michelle Michels, Sumeet S. Mitter, Jesus E. Pino Moreno, Iacopo Olivotto, Anjali T. Owens, Steen H. Poulsen, Florian Rader, Ethan J. Rowin, P. Christian Schulze, Robert Sepp, Nikhil Sikand, Scott D. Solomon, John A. Spertus, Charles Teale, Sr., Xiaoyan Zhao, Punag H. Divanji, Stephen B. Heitner, Daniel L. Jacoby, Stuart Kupfer, Fady I. Malik, Joel Salazar-Mendiguchía, Amy Wohltman, Shu Zhuo and Carolyn Y. Ho, 27 August 2026, New England Journal of Medicine.
DOI: 10.1056/NEJMoa2603021
“Effect of Aficamten on Cardiac Structure and Function in Patients with Symptomatic Nonobstructive Hypertrophic Cardiomyopathy” by Sheila M. Hegde, Xiaowen Wang, Ankit Bhatia, Maria Luisa Peña-Peña, Mark V. Sherrid, Estevao Lanna Figueiredo, Michael Arad, Roberto Barriales-Villa, Lubna Choudhury, Brian L. Claggett, Caroline J. Coats, Edileide de Barros Correia, Juan Pablo Costabel, Perry M. Elliott, Jorge E. Silva Enciso, Pablo Garcia-Pavia, Junbo Ge, Carolyn Y. Ho, Neal K. Lakdawala, Gregory D. Lewis, Martin S. Maron, Matthew W. Martinez, Ahmad Masri, Mathew S. Maurer, Michelle Michels, Sumeet S. Mitter, Jesus E. Pino Moreno, Viktória Nagy, Iacopo Olivotto, Anjali T. Owens, Steen H. Poulsen, Florian Rader, Ethan J. Rowin, Maria Ruda, P. Christian Schulze, Nikhil Sikand, John A. Spertus, Xiaoyan Zhao, Punag H. Divanji, Stephen B. Heitner, Daniel L. Jacoby, Stuart Kupfer, Fady I. Malik, Joel Salazar-Mendiguchía, Amy Wohltman, Shu Zhuo and Scott D. Solomon, 29 August 2026, Circulation.
DOI: 10.1161/CIRCULATIONAHA.126.082343
Cytokinetics, maker of aficamten, supported both studies.
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