More details from the Phase III GALACTIC-HF trial were presented at the American Heart Association (AHA) Scientific Sessions showing that heart failure patients with reduced ejection fraction (HFrEF) who took omecamtiv mecarbil had a significant 8% relative risk reduction on the primary composite endpoint of HF events or cardiovascular (CV) death, compared to placebo, Cytokinetics announced Friday. The company, which is co-developing the experimental cardiac myosin activator together with Amgen, reported last month that the study had met its main goal, but that the drug was no better than placebo on a key secondary endpoint that looked at CV death alone.
GALACTIC-HF enrolled 8256 patients with class II-IV HFrEF and a left ventricular ejection fraction (LVEF) of 35% or less. Subjects were randomised to either oral placebo, or a 25-mg starting dose of omecamtiv mecarbil twice daily, with maintenance doses of 25 mg, 37.5 mg or 50 mg, also administered twice a day. Cytokinetics noted that the trial included both inpatients and outpatients, and also had a "high representation" of participants with moderate-to-severe HF symptoms, as well as lower ejection fraction, systolic blood pressure and renal function.
The primary composite endpoint was time to CV death or first HF event, comprising HF hospitalisation and other urgent treatment for HF. Secondary goals were time to CV death, patient-reported outcomes as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) total symptom score (TSS), time to first HF hospitalisation and time to all-cause death.
Updated findings presented at the AHA conference, and also simultaneously published in the NEJM, showed that during a median of 21.8 months, a primary-outcome event occurred in 37% of patients in the omecamtiv mecarbil group and in 39.1% of those in the placebo arm. Cytokinetics noted that this effect was observed "without evidence of an increase in the overall rates of myocardial ischaemic events, ventricular arrhythmias or death from CV or all causes." The company also said benefits of the drug were consistent across most subgroups, with a potentially greater treatment effect among patients having an LVEF of 28% or less. Omecamtiv mecarbil also significantly decreased NT-proBNP concentrations by 10% at week 24 compared to placebo.
However, there was a slight increase in mortality rate among patients treated with omecamtiv mecarbil in the study, with 19.6% dying from CV causes, compared with 19.4% for placebo. Further, there was no significant difference between groups in the change from baseline on the KCCQ total symptom score. "No other secondary endpoints were met in accordance with the prespecified statistical analysis," Cytokinetics said.
Meanwhile, there were no significant imbalances in adverse events between patients in either the treatment or placebo groups. In addition, researchers noted that side effects that typically limit the use of current HF therapies, such as adverse effects on blood pressure, heart rate, potassium levels or kidney function, were not observed.
When top-line results were released last month, Citi analysts said the GALACTIC-HF results fell short of clearing a commercial and clinical hurdle that Amgen and Cytokinetics had previously set for the drug to be competitive, and that they doubted Amgen would want to move forward with a launch. On Friday, Cytokinetics' R&D head Fady Malik remarked "we look forward to continuing to discuss next steps in this programme with Amgen to inform a potential path forward."
Amgen holds an exclusive global license to omecamtiv mecarbil, which is also known as CK-1827452 and as AMG 423, and is partnered with Servier for exclusive marketing rights to the drug in Europe, as well as the Commonwealth of Independent States, including Russia. The FDA issued a fast-track designation for omecamtiv mecarbil in May as a potential treatment for chronic HFrEF.
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