Amgen and Cytokinetics did not impress when they unveiled topline data for their heart failure drug last month. Now, the duo are sharing a deeper look at a treatment that met its goal in a phase 3 study but did not help patients with heart failure live longer.
The study, GALACTIC-HF, was presented virtually on Friday at the annual meeting of the American Heart Association. It tested three dose levels of the drug, omecamtiv mecarbil against placebo in more than 8,200 patients who had heart failure with reduced ejection fraction (HFrEF), a type of heart failure where the heart muscle does not contract effectively, so less oxygen-rich blood gets pumped out to the body. About 7% of the patients were Black, while more than three quarters were white (78%) and male (79%).
The study met its primary endpoint reducing the amount of time until patients either died from heart-related causes or needed treatment for heart failure by 8%. The investigators called this improvement a “modest but significant lowering” of the risk of death, hospitalization or urgent treatment for heart failure.
However, omecamtiv mecarbil didn’t move the needle on the study’s secondary endpoints, namely time to first hospitalization, death from heart-related causes, death from any cause, and change from baseline on the Kansas City Cardiomyopathy Questionnaire. The questionnaire measures how patients perceive their health status, including their heart failure symptoms and how they affect their quality of life, and physical and social function.
“The lack of effect on death from either cardiovascular causes or any cause is surprising, given the prior evidence with omecamtiv mecarbil of improvements in left ventricular volumes and function, as well as decreases in heart rate and NT-proBNP,” a hormone linked to worsening heart failure, the investigators wrote.
Side effects occurred at roughly the same rates in both groups. About 9% of patients in each group quit the study because of side effects. The results appear in the New England Journal of Medicine.
Amgen and Cytokinetics weren’t particularly upbeat last month when they reported the topline data. The results “further the understanding” of the treatment of heart failure, and the study “provides insights” into the mechanism of action of omecamtiv mecarbil, Amgen and Cytokinetics’ R&D chiefs, David Reese, M.D., and Fady Malik, M.D., Ph.D., said in a statement at the time.
The data were “underwhelming” and a “GALACTIC Disappointment,” JPMorgan analyst Cory Kasimov wrote in a note to clients at the time, adding that missing the secondary endpoint “casts doubt on the outlook of this product candidate.”
Developed at Cytokinetics, omecamtiv mecarbil is a cardiac myosin activator, meaning it boosts interactions between myosin heads and actin filaments in the heart muscle to in turn boost the pumping of the heart. The company teamed up with Amgen in 2006 to develop heart failure drugs, and the Big Biotech later licensed the global rights to omecamiv mecarbil. In 2013, French pharma Servier picked up the rights to market the drug in Europe.
Merck and Bayer have seen similar results with their own heart failure med, vericiguat. In a phase 3 study that enrolled more than 5,000 patients, the drug statistically did no better than placebo at reducing deaths, but it did beat placebo on its primary endpoint: decreasing a composite measure of deaths and hospitalizations for heart failure. Despite the mixed data, the FDA granted the drug a speedy review in July and plans to decide its fate by January 2021. For its part, omecamtiv picked up a “fast-track” tag from the FDA in May of this year.