For decades, drugmakers have been confounded in the clinic by a rare form of hypertrophic cardiomyopathy. But with the released of detailed data behind the landmark Acacia trial, Cytokinetics is demonstrating first-of-its-kind benefits in the condition and potentially paving the way for a watershed FDA approval.
The drugmaker’s cardiac myosin inhibitor, Myqorzo (aficamten), is the first to demonstrate significant, clinically meaningful benefits in patients with a rare heart condition called non-obstructive hypertrophic cardiomyopathy (nHCM).
In patients with nHCM, the heart’s pumping muscles become thick and stiff, preventing the organ from relaxing enough to properly refill with blood. To date, the standard of care for nHCM patients has been extrapolated from other, larger cardiac trials—including options such as off-label beta blockers, calcium channel blockers, or antiarrhythmic drugs—and has been unsupported by concrete data.
But the Acacia trial—to be presented in depth at the European Society of Cardiology Congress in Munich this weekend—offers long-awaited evidence for a new potential treatment for nHCM.
According to the data, patients on Myqorzo charted a 3-point higher improvement in KCCQ-CSS, a patient-reported survey used to evaluate symptoms and limitations of those with heart conditions, compared to placebo at 36 weeks. Patients who remained on the treatment until 72 weeks saw a 7-point advantage.
Compared with placebo at 36 weeks, the treatment group also saw a 0.67ml/kg/min improvement in peak oxygen uptake (pVO2), a measure of maximum exercise capacity. Previous work by Cytokinetics in obstructive hypertrophic cardiomyopathy (oHCM) suggests that patients could start experiencing a functional improvement at a 0.35 increase in pVO2; Myquorzo nearly doubled that threshold in the nHCM trial.
“This is huge. If you’re a patient with non-obstructive hypertrophic cardiomyopathy, you can only imagine how exciting this is,” Stephen Heitner, M.D., Cytokinetic’s chief medical officer, told Fierce. Together, these data are proof of improvement in both “feel and function,” he said. “Patients reported feeling better and they were able to objectively exercise more after having the aficamten relative to placebo.”
At the end of 72 weeks, Cytokinetics conducted a 4-week washout, halting both treatments. Without Myqorzo, the treatment arm’s KCCQ-CSS score dramatically declined to match the placebo group, offering a sort of “reverse proof” of the medicine’s benefit, Heitner said.
The treatment also helped patients charge significant improvements on secondary endpoints like the New York Heart Association Functional Class—a clinical measure of heart failure severity and cardiopulmonary exercise testing— and NT-proBNP, a measure of cardiac stress.
The success comes after Bristol Myers Squibb’s Camzyos came up short in a similar trial for nHCM last year. Camzyos was the first of the cardiac myosin inhibitors to enter the market, approved in 2022 for oHCM, giving it a significant lead on Cytokinetics’ 2025 approval in the same indication. An approval in nHCM, however, would allow Cytokinetics to gain some ground, potentially doubling the potential patient population for which Myquorzo can be prescribed.
While it’s rare by diagnosis rate, nHCM is still reported to be prevalent in somewhere between 1 in 200 and 1 in 500 people, Heitner told Fierce.
On the safety front, Myqorzo was well-tolerated in the trial. Seven percent of enrollees on Myqorzo discontinued the drug early due to adverse events compared to 1.9% on placebo.
As expected, the drug was linked to increased risk of heart failure. The drug already carries a boxed warning following its 2025 approval, and Cytokinetics manages an FDA-mandated risk evaluation and mitigation strategy (REMS) to minimize the risk of heart failure.
The drug ultimately reduces the contractility of the heart muscles to a more normal level, Heitner said. “The problem is there are some patients that if you reduce contractility either too much or too quickly, you can overshoot the mark,” he explained.
The relaxation effect can weaken the heart more than intended to the point of heart failure. In the trial, only two participants (0.8%) in the Myqorzo group progressed to heart failure associated with the drug’s relaxing effect. Twenty-seven participants’ (10.5%) left side ejection fraction (LVEF), a measure of contractility, dipped below the predetermined threshold of 50%. Of those, 21 were able to continue the study with dose adjustments.
In what Heitner called an imbalance in the study, ten additional participants in the Myqorzo arm went into heart failure unrelated to a decreased LVEF, compared to three in the placebo group. All of the heart failure cases happened early in the study during dose titration.
Heitner attributed this to early dosing decisions made by an AI algorithm that adjusted the dose based on ejection fraction alone, but not on how a patient was feeling. In the continuation study, physician judgment was used for prescribing instead, and the heart failures unrelated to ejection fraction dropped to two out of 390 patients.
Acacia data in hand, Cytokinetics is moving ahead with plans to file for FDA supplemental approval for nHCM by the end of Q4. Myqorzo is already available in the U.S. and China as a treatment for oHCM.
Cytokinetics also boasts approvals in the United Kingdom and the EU, where the company is staggering its Myqorzo rollouts, starting with Germany this past June.