dm+d

Unassigned

New Medicines

Chronic heart failure in patients with left ventricular systolic dysfunction and reduced ejection fraction [2].

Information

New molecular entity
Cytokinetics
Cytokinetics

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Pre-registration (Filed)
Jun 22FDA have extended PDUFA date by three months to 28 Feb 23, the decision stems from the submission of additional pharmacokinetic analyses, which the agency deemed to be a major amendment to the new drug application [30].
Apr 22In its latest annual report, Cytokinetics states that it will need to seek a replacement partner in Europe with the expertise and resources to successfully launch and commercialise omecamtiv mecarbil in Europe or to establish its own commercial capabilities in Europe [28].
Feb 22FDA accept NDA for the treatment of heart failure with reduced ejection fraction and assign a PDUFA date of 30/11/22 [25].
Aug 21Cytokinetics conducts a pre-NDA meeting with the US FDA regarding NDA submission for HF based on the GALACTIC-HF trial [24]
May 21Cytokinetics has a goal of filing with FDA by the end of this year [22].
Mar 21Cytokinetics announces it intends to meet the FDA to discuss results of the GALACTIC-HF trial in Q1 2021 [21].
Dec 20After evaluating the GALACTIC-HF trials, Servier has provided Amgen with the notice of termination of its sub-licence to develop and commercialise omecamtiv mecarbil in the EU. Servier has no plans to bring this to the UK [20].
Nov 20Amgen is handing omecamtiv mecarbil development back to Cytokinetic following a PIII study that showed that the drug failed to improve survival [19].
May 20Granted fast track status in US [16].
Jan 19The PIII GALACTIC-HF trial is still recruiting subjects, with an estimated primary completion date of Jan 21. The METEORIC-HF (NCT03759392) is not yet recruiting subjects. [12]
Jan 18Amgen and Cytokinetics plan a second phase III trial in Heart failure in 2018 [11]
Feb 17Amgen has an alliance with Servier for exclusive commercialisation rights in Europe [10].
Nov 16Amgen, in collaboration with Cytokinetics initiated a phase III, GALACTIC-HF (Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure) registrational study (NCT02929329) to assess the efficacy and safety of omecamtiv mecarbil on mortality and morbidity in subjects with CHF (NYHA class II to IV) with reduced ejection fraction (LVEF = 35%). The trial will enrol approximately 8,000 patients in the US and EU. The primary endpoint is a composite of time to cardiovascular death or first heart failure event. The estimated primary completion date is March 2021 [9].
Sep 16Cytokinetics and Amgen have announced that they intend to advance omecantiv to PIII development, with expected initiation late 2016 [7]; however it is not yet known whether the proposed trial design has been agreed with regulators [8].
May 16During Q1 16, Cytokinetics participated with Amgen in regulatory meetings with the FDA, EMA and Health Canada intended to inform the design of a potential PIII development program for omecamtiv mecarbil. They also conducted various clinical, non-clinical and planning activities in collaboration with Amgen, & expect to make a decision regarding the advancement to PIII in the coming months [6].
Nov 15Positive PII data positions omecamtiv as a player to watch in Amgen´s cardio pipeline, though it still has a very long way to go [4].
Oct 15During Q1 of 2015, Cytokinetics collaborated with Amgen to progress development of omecamtiv mecarbil to PIII [3].

Category

Activator of cardiac myosin - increases cardiac contractility (modified release formulation)
A UK survey of heart failure management in general practice found an average prevalence of 8.3 per 1,000 population. Prevalence is increasing due to ageing populations and improved survival after coronary events and secondary prevention [1].
Chronic heart failure in patients with left ventricular systolic dysfunction and reduced ejection fraction [2].
Oral

Further information

Yes

Trial or other data

Jul 22PIII METEORIC-HF RCT (n=276) found omecamtiv mecarbil did not improve peak oxygen uptake (V̇o2) from baseline over 20 weeks vs placebo (mean, −0.24 vs 0.21 mL/kg/min; least square mean difference, −0.45 mL/kg/min; 95% CI, −1.02 to 0.13; P = 0.13), and does not support use in this setting [31].
May 22PIII GALACTIC-HF study found that compared to placebo omecamtiv mecarbil reduced primary outcome of time to CV death or first heart failure event in patients with systolic blood pressure (SBP) ≤100 mmHg (n=1,473; HR; 0.81; 95% CI, 0.70-0.94) but not those with SBP >100 mmHg (n=6,759; 0.95; 0.88-1.03) [29].
Apr 22Additional data from the GALACTIC-HF study demonstrates a 19% reduction in costs per pt among those who received omecamtiv mecarbil. Of the expense reductions, around 99% were because the drug had helped pts avoid hospitalisations related to heart failure [27]
Feb 22In the most recent PIII trial (METEORIC-HF; NCT03759392), omecamtiv mecarbil did not beat placebo at improving cardiopulmonary exercise testing after 20 weeks of treatment in patients with HFrEF [26].
Oct 21Post hoc analysis of GALACTIC-HF RCT (n=2258 of 8232) suggests patients with severe heart failure (HF) experienced significant treatment benefit for primary end point (HR 0.80; 95% CI, 0.71-0.90) which was not evident in patients without severe HF [23].
May 21METEORIC has completed enrollment and a data read out is expected in 2022 [22].
Nov 20PIII GALACTIC-HF study (n=8256) found among patients with heart failure and reduced ejection, those on omecamtiv mecarbil had lower incidence of composite of a heart-failure event or death from CV causes than those who received placebo (37% vs. 39.1%; respectively, 0.92; 95% CI, 0.86- 0.99; p=0.03) [18].
Oct 20PIII trial GALACTIC-HF results found treatment with omecamtiv mecarbil achieved statistically significant primary composite efficacy endpoint in reducing cardiovascular (CV) death or heart failure events (heart failure hospitalization and other urgent treatment for heart failure) compared to placebo in patients treated with standard of care (HR: 0.92; 95% CI: 0.86, 0.99, p=0.0252). No reduction in the secondary endpoint of CV death was observed [17].
Apr 20PIII GALACTIC-HF study (NCT02929329) is due to complete collection of primary outcome data in Aug 20. The purpose of this registrational study is to determine if treatment with omecamtiv mecarbil/AMG 423 when added to standard of care is well tolerated and superior to placebo in reducing the risk of cardiovascular death or heart failure events in subjects with chronic HFrEF. 8,256 patients will be enrolled [15].
Nov 19In COSMIC-HF, 448 pts with stable, symptomatic HF and LVEF <40% on omecamtiv mecarbil [25 mg twice daily (n=150); or 25 mg twice daily with pharmacokinetic-guided dose selection to 50 mg twice daily (PK group, n=149)] or placebo (n=149) for 20 weeks were assessed for the effect on echocardiographic measures of diastolic function. In pts with HFrEF on omecamtiv, systolic ejection time increased while diastolic filling time was not reduced, nor were diastolic parameters worsened.[14]
Feb 19PIII METEORIC-HF trial (NCT03759392) starts, to evaluate the effect of treatment with omecamtiv mecarbil compared to placebo on exercise capacity as determined by cardiopulmonary exercise testing (CPET) in patients with HFrEF [13].
Nov 15Amgen reported that the expansion phase of the COSMIC-HF trial met its primary pharmacokinetic endpoints and demonstrated statistically significant improvement in all the secondary measures of cardiac function [4].
Oct 15Data from the expansion phase of COSMIC-study showed statistically significant improvements in several measures of cardiac function, including systolic ejection time, stroke volume and N-terminal-pro-brain natriuretic peptide at 20 weeks post randomisation. The effects of omecamtiv mecarbil were generally dose dependent. Adverse events, including serious adverse events were omecamtiv mercarbil were comparable to those on placebo. A small increase in troponin was seen among pts receiving omecamtiv mecarbil but this was not determined to be related to myocardial ischemia or infarction. There was no imbalance in deaths, and cardiac adverse events were generally balanced between placebo and active treatment groups [2,3].
Jan 13Amgen and Cytokinetics initiated a randomised, double-blind PII trial of oral modified release (MR) omecamtiv mecarbil in pts with heart failure and left ventricular systolic dysfunction; the Chronic Oral Study of Myosin Activation to Increase Contractility in Heart Failure, (COSMIC-HF; NCT01786512) study. The first part of the trial was a dose-escalation study, aimed at characterising the pharmacokinetics of omecamtiv mecarbil in ~420 pts in the US and Hungary. The results of the first part informed dosing for the longer expansion phase of the trial. In the dose escalation phase, pts were randomised 1:1:1 to placebo or omecamtiv mecarbil (MR) (25 mg twice daily or 50 mg twice daily) for 35 days. The expansion phase evaluated 448 chronic heart failure pts with reduced ejection fraction who were given omecamtiv mecarbil for 20 weeks and followed for a 24 weeks. The primary endpoints for the expansion phase were to assess the maximum and pre-dose plasma concentration of omecamtiv mecarbil. Safety and tolerability were evaluated as secondary endpoints to week 24. COSMIC-HF was not designed to assess the impact of omecamtiv mecarbil on cardiovascular outcomes in heart failure pts [2,3].

Evidence based evaluations