AHA: Analysis counters concerns about Amgen heart failure drug

Amgen Headquarters
Amgen's headquarters (Amgen)

Amgen has found no evidence that heart failure drug omecamtiv mecarbil hampers diastolic function in a post hoc analysis of phase 2 data. The finding may quell concerns that the effect of the cardiac myosin activator on the cardiac cycle will have negative side effects on diastolic filling times.

In recent years, researchers at groups other than Amgen have published papers on the potential for omecamtiv mecarbil to impair diastolic function. Interest in the topic stems from the mechanism of the drug, which increases interactions between myosin heads and actin filaments to boost pumping of the heart. The concern is that increased pumping will come at the expense of diastolic filling time.

Amgen is developing omecamtiv mecarbil with Cytokinetics and Servier. 

To assess whether the clinical data support those concerns, the companies performed a post hoc analysis of results from a 448-patient phase 2 trial that originally read out several years ago. The analysis looked at echocardiographic measures of diastolic function.

Amgen found no statistically significant difference between omecamtiv mecarbil and placebo on most measures of diastolic function. Diastolic filling time was comparable in the treatment and control arms, as were several other relevant parameters. 

One exception was isovolumic relaxation time (IVRT), which increased in the two omecamtiv mecarbil cohorts by statistically significant amounts over placebo. However, the effect was fairly small. In the treatment groups, IVRT ticked up by close to 5 ms from baseline figure of 101 ms and 105 ms. IVRT in the control arm declined slightly from a baseline of 100 ms. Grade 1 diastolic dysfunction is associated with prolonged IVRT.

The post hoc analysis also identified a statistically significant difference in tricuspid regurgitation velocity (TRV) in one of the two treatment arms. TRV improved in the pharmacokinetic-guided dose selection cohort but not in the fixed dose or placebo groups.

Tor Biering-Sørensen, the University of Copenhagen associate professor who is presenting the data at the American Heart Association’s annual Scientific Sessions, framed the results as a positive for the drug. 

“The results show that, in addition to increasing the pumping action of the heart, omecamtiv mecarbil did not change and for some measures was consistent with improvement of the heart’s diastolic function, or ability to relax between heartbeats,” Biering-Sørensen said in a statement.

More comprehensive assessments of the effects of omecamtiv mecarbil are underway. One of the phase 3 trials, GALACTIC-HF, came through a futility analysis earlier this year and enrolled its final patient shortly thereafter. The trial is assessing the effect of omecamtiv mecarbil on the time to heart failure or cardiovascular death. A second phase 3 is assessing the drug’s effect on exercise capacity.