Cytokinetics recently reported additional data from its phase 3 MAPLE-HCM study, which evaluated the use of aficamten compared to standard of care (SOC) metoprolol for the treatment of patients with hypertrophic cardiomyopathy (HCM). It noted that its drug was able to beat SOC in these patients with respect to a few measures, which were improvement in the structure of the heart muscle and the functioning of it. Such positive results were shown at the European Society of Cardiology Congress 2025 and were also published in a medical journal known as the “Journal of the American College of Cardiology.” This data affirms that aficamten is able to help treat these patients with HCM.
Hypertrophic Cardiomyopathy (HCM), or wall thickening, occurs in the wall between the two ventricles (chambers of the heart). These two ventricles are known as the left ventricle and right ventricle, respectively. Furthermore, it is important to distinguish the subpopulation that was being targeted in the late-stage MAPLE-HCM trial. The patients were those who had obstructive HCM, which means that blood outflow is hindered in these patients. However, they had to suffer from left ventricular outflow tract (LVOT) obstruction of said blood flow during exercise capacity.
This wasn’t the first time that the company had shown its drug aficamten to be superior to that of metoprolol, as such a finding was previously shown with the release of the primary efficacy endpoint finding back on May 13, 2025. At that time, it was revealed that the primary endpoint of change in peak oxygen uptake (pVO2) from baseline to week 24, between drug versus placebo, was met with statistical significance. This was an important finding as it relates to these patients’ exercise capacity. That’s because this efficacy endpoint evaluates the peak level of oxygen obtained when a patient is at the maximum point in exercise. Again, it was shown here that aficamten was superior to SOC metoprolol.
Metoprolol works by having two mechanisms in place, which are to reduce heart rate and to also lower the heart’s contractility (expandability). The reason for doing these two intended functions is to give the heart more time to fill up with blood before it pumps it out. This move is thought to help these patients with obstructive HCM. The bottom line here is that aficamten can set a new standard in treating these patients and could be highly welcomed. To further prove this point, Cytokinetics’ cardiac myosin inhibitor aficamten was able to reduce wall thickness by a greater margin compared to metoprolol. That is the difference established between both of these treatments, which was that of -1.01 mm.
This may seem small, but it goes back to what I noted about HCM, which involved a thicker wall that causes symptoms in these patients. It appears as though Wall Street was quite impressed with this updated MAPLE-HCM data because the stock closed higher on September 2, 2025, by 40.45% to around $49.62 per share. The updated data from this late-stage trial shows how well this drug compared to current SOC. More importantly, though, there is a key catalyst for investors to keep an eye on before the end of this year. This would be the expected Prescription Drug User Fee Act target action date of December 26, 2025. The FDA is expected to decide on or before this date for the approval of aficamten to treat patients with obstructive HCM.
Before this, though, there is a late-cycle meeting that is expected to happen during this month of September of 2025. Originally, the PDUFA target action date of aficamten for this group of HCM patients was supposed to be decided upon in September of 2025. However, Cytokinetics didn’t submit a risk evaluation mitigation strategy (REMS) with the filing of the NDA; thus, the FDA gave notice that it had to extend the time for its review of this drug. Typically, if it were a minor application issue, then such a delay wouldn’t have happened. But the time needed to review the REMS with the NDA required a lot more time and thus, the reason for the delay.
It remains to be seen if the company gets its drug aficamten approved to treat these obstructive HCM patients, but it is already in the process of expanding the possible patients it could go after. For instance, it is in the process of running the late-stage study ACACIA-HCM, which is intended to target patients with non-obstructive HCM. These patients still have the thickened heart muscle wall issue but don’t have the blood flow obstruction observed in those with obstructive HCM. With that being said, it is not going to be long before a look of data is to be viewed from this trial, because data from it is expected in the first half of 2026. This study also has a cohort of patients in Japan, but since this portion was just dosed, the data won’t be available with the U.S. data.
Plus, it is looking at using this cardiac myosin inhibitor to also target pediatric patients with obstructive HCM using the phase 3 CEDAR-HCM clinical trial. The science of aficamten is ideal because it binds to an allosteric (distinct) site on myosin, and the entire purpose is to change the heart muscle’s contractility. In essence, it allows the heart muscle a greater window of being in a relaxing state. The decrease of the cardiac myosin ATPase activity, along with the slower than expected release of phosphate from ATP hydrolysis, results in the restful myosin I just noted and subsequent reduced contractility of the heart.
Beyond aficamten, Cytokinetics is still in the process of moving forward with a phase 3 study known as COMET-HF, which is instead using the cardiac myosin activator omecamtiv mecarbil to treat patients with symptomatic heart failure (HF) with severely reduced ejection fraction. It expects to complete enrollment for this specific program in late 2026.