New Data Offers Insight into HFrEF Patient Risk, Treatment Potential

October 7, 2020

Cytokinetics announces presentations on two trials assessing omecamtiv mecarbil in patients with heart failure and reduced ejection fraction.

Real-world heart failure patients that were representative of those enrolled in the Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure (GALACTIC-HF) Phase 3 trial were considered a high-risk population with significant unmet need, according to a study presented at the Heart Failure Society of America (HFSA) Virtual Annual Scientific Meeting 2020.

The GALACTIC-HF study was an event driven cardiovascular outcomes clinical trial that assessed omecamtiv mecarbil in heart failure patients with reduced ejection fraction.

Investigators from Cytokinetic used de-identified electronic health records from 2006-2016 to conduct an analysis of outcomes in real-word heart failure patients with characteristics similar to the trial population.

Patient records reflected inpatients and outpatients at the Vanderbilt University Medical Center and were separated into 2 cohorts.

The clinical cohort included 3955 patients who matched the eMERGE network phenotype of HFrEF, with a left ventricular ejection fraction (LVEF) ≤ 40%.

A GALACTIC-HF-like cohort included 1541 patients who had matched eligibility criteria of those in trial. These criteria included hospitalizations, medications, laboratory values, and LVEF ≤ 35%.

Thus, about 40% of real-world HFrEF patients from their database had met the eligibility criteria for the GALACTIC-HF trial.

The median age at index data for the clinical cohort was 65, and 61 for the GALACTIC-HF-like cohort. Further, both cohorts were about 66% male and 80% white.

Blood pressure and heart rate were similar between the groups, but the GALACTIC-HF-like cohort demonstrated a higher median N-terminal B-type (NT-proBNP) level (821 pg/m) compared with the clinical cohort (506 pg/mL).

The investigators also noted that comorbidities were slightly higher in the GALACTIC-HF-like group. These comorbidities included chronic kidney disease (31% vs 21% in clinical group) and atrial fibrillation (32% vs 23%).

Higher rates of utilization of cardiac resynchronization or implantable cardioverter defibrillator were also noted in the GALACTIC-HF-like cohort than the clinical group (26% vs. 23%, respectively).

And finally, the heart failure hospitalization rate (per 1000 patient-years) was 396 (95% CI, 350-442) in the GALACTIC-HF-like cohort and 242 (95% CI, 203-280) in the clinical cohort during median follow up of 4.1 and 2.7 years, respectively.

Also presented at HFSA 2020 were results from a post-hoc analysis of the Chronic Oral Study of Myosin Activation to Increase Contractility in Heart Failure (COSMIC-HF) study, a Phase 2 clinical trial that evaluated omecamtiv mercarbil in patients with HFrEF.

These results suggested that the treatment improved right ventricular function in these patients.

Originally, the double-blind study had assessed left atrial and ventricular function in patents with stable, symptomatic heart failure and an LVEF <40%.

All 48 patients were randomly assigned 1:1:1 to receive 25 mg of omecamtiv mecarbil twice daily, 25 mg - 50 mg of the same treatment twice daily with pharmacokinetic-guided dose selection (or PK titration group), or placebo for 20 weeks.

The post-hoc analysis found that patients in the PK titration group demonstrated improved measures of right ventricular function.

These measures included right ventricular systolic ejection time (RV-SET) (P<.001), right ventricular end-systolic area (RV-ESA) (P = .012), and right ventricular outflow tract velocity time integral (RVOT-VTI) (P = .002).

Additionally the analysis showed improvements in measures of right ventricular pulmonary arterial coupling.

“These analyses of real-world patients comparable to those in GALACTIC-HF and who are at high risk of cardiovascular events including hospitalization support the design of our Phase 3 clinical trial to assess the potential of omecamtiv mecarbil in patients with clinical unmet need,” said Fady I. Malik, M.D., Ph.D., Cytokinetics’ Executive Vice President of Research & Development in a statement.

“Additionally, while we have previously reported that treatment with omecamtiv mecarbil improved left atrial and ventricular function in patients in COSMIC-HF, these additional data suggest that right ventricular function may have been improving as well, underscoring a potential for a more comprehensive effect on overall cardiac function.”