Metoprolol Tartrate

istock, Alona Horkova Data from the late-stage MAPLE-HCM study position Cytokinetics’ cardiac myosin inhibitor aficamten as a potential first-line therapy for patients with obstructive hypertrophic cardiomyopathy. Cytokinetics’ aficamten significantly improved exercise capacity in a Phase III study of patients with obstructive hypertrophic cardiomyopathy, sending the biotech’s shares soaring 40% on Tuesday morning. The data from the MAPLE-HCM study, presented at the 2025 European Society of Cardiology Congress on Saturday, showed that after 24 weeks of treatment, patients on aficamten saw a 1.1-mL/kg/min increase in pVO2, a measure of oxygen supply that indicates exercise capacity. Counterparts on the standard-of-care beta-blocker metoprolol, meanwhile, saw a 1.2-mL/kg/min decrease in pVO2 over the same time span. Writing to investors on Monday, analysts at Truist Securities said that these findings position aficamten as a “potentially best-in-class” cardiac myosin inhibitor for obstructive hypertrophic cardiomyopathy (HCM), adding that the data support a first-line indication for the drug. “Beta blockers have been the standard of care in [the first-line setting] for HCM for the past several decades despite limited evidence and. . .feedback indicating lack of consistent and broad efficacy,” Truist wrote. MAPLE-HCM’s data are “robust,” the analysts added, noting that outperforming metoprolol could help aficamten stand out in the HCM space. Designed to be taken orally, aficamten is a selective blocker of cardiac myosin, a protein involved in the contraction of the heart muscles. This mechanism of action allows the drug to suppress the hypercontraction of the heart, a symptom typical of HCM. Cytokinetics in December 2024 filed for the approval of aficamten in obstructive HCM, which the FDA gave an initial action date of Sept. 26, 2025. In May this year, however, the regulator pushed back its decision deadline by three months in order to review a follow-on submission regarding risk management. A verdict is now expected by Dec. 26 . Data from MAPLE-HCM were not part of Cytokinetics’ original submission, and the company plans to findings in the future, according to Truist. With Saturday’s readout, Cytokinetics gains ground on Bristol Myers Squibb, which owns Camzyos , a similar cardiac myosin inhibitor approved for obstructive HCM. In April this year, the pharma reported that the drug failed the Phase III ODYSSEY-HCM study, unable to best placebo at improving exercise capacity at 48 weeks in patients with non-obstructive disease. Camzyos also did not result in significantly better symptoms and physical function versus placebo.

Cytokinetics unveiled full results from the Phase III MAPLE-HCM trial on Saturday, showing its investigational therapy aficamten outperformed metoprolol, a beta blocker that has served as the default treatment for obstructive hypertrophic cardiomyopathy (oHCM) for decades. The findings, presented at the European Society of Cardiology (ESC) meeting and published in the NEJM, may trigger what CEO Robert Blum called a "provocative conversation" about the standard of care in the disease.Aficamten is currently under review at the FDA as a potential treatment for oHCM based largely on data from the Phase III SEQUOIA-HCM study comparing it against placebo. A decision on the cardiac myosin inhibitor originally expected in September was recently pushed to December 26.MAPLE-HCM, which was toplined in May, pitted aficamten against beta blockers as monotherapy in patients with symptomatic oHCM. The cardiac myosin inhibitor outperformed metoprolol across nearly every measure, according to Cytokinetics.Rethinking the standardIn the 175-patient study, aficamten significantly improved peak oxygen uptake (pVO₂) by an average of +1.1 mL/kg/min over 24 weeks, while those on metoprolol worsened by -1.2 mL/kg/min, yielding a 2.3 mL/kg/min difference. The superiority of aficamten held consistent across prespecified subgroups, including newly diagnosed or treatment-naïve patients, the company said.Most secondary outcomes also favoured aficamten. More than half (51%) of patients in the aficamten arm experienced at least a one-class improvement in NYHA functional class versus 26% on metoprolol. Quality-of-life improved as well, based on a 6.9-point superior change in KCCQ Clinical Summary Score. Aficamten also produced a significant 81% reduction in the NT-proBNP cardiac biomarker, and significantly lowered resting and Valsalva left ventricular outflow tract gradients. The only endpoint without statistical significance was left ventricular mass index."MAPLE-HCM provides the field its first look at a cardiac myosin inhibitor compared directly to a beta-blocker," remarked lead author Pablo Garcia-Pavia. "These results call into question the reliance on beta-blockers as the initial treatment modality for obstructive HCM that has prevailed for over 60 years."Ahead of the readout, Blum predicted the MAPLE-HCM data "will be a quite provocative conversation…because it really does call into question something that's been standard of care for decades."Challenging CamzyosAdverse events were similar in the two treatment groups, though safety data appeared to tilt in aficamten's favour. Down-titration was required in four (4.5%) aficamten patients – three for left ventricular ejection fraction (LVEF) < 50%, one for dizziness – compared to 26 metoprolol patients (nearly 30%) due to low systolic blood pressure, bradycardia or other effects. One death occurred in the aficamten group (a 69-year-old woman with multiple co-morbidities who developed a viral illness). Hypertension was more common with aficamten (10.2% vs. 2.3%), while dizziness was higher in the metoprolol group (17.2% vs. 5.7%).The MAPLE-HCM results could help aficamten stand out against Bristol Myers Squibb's first-to-market cardiac myosin inhibitor Camzyos (mavacamten) in the obstructive HCM space. Approved by the FDA in 2022, Camzyos received updated labelling earlier this year that reduced some of its monitoring requirements and eased certain restrictions.However, BMS announced in April that Camzyos had failed to meet the co-primary endpoints in the Phase III ODYSSEY-HCM trial in patients with non-obstructive HCM (see – Spotlight On: BMS setback may clear path for Cytokinetics to distinguish aficamten across HCM).