Amgen and Servier have decided to run a second phase 3 trial of omecamtiv mecarbil in heart failure, as their first pivotal study counts down towards a readout.
Originally developed by Cytokinetics, omecamtiv is the first in a new class of drugs designed to increase the duration of cardiac muscle contractility and improve cardiac muscle performance in heart failure. It is one of a handful of new drugs in late-stage development for the disease, which has seen very few advances in treatment in the last few decades.
The new trial – dubbed METEORIC-HF – will compare omecamtiv to placebo in patients with heart failure with reduced ejection fraction (HFrEF), which occurs when the left side of the heart isn't able to pump blood out to the body effectively. It is the most common form of heart failure.
The decision to press ahead with a second trial of omecamtiv in HFrEF suggests Amgen, Servier and Cytokinetics are optimistic about the outcome of the their already-running GALACTIC-HF study, which is due to complete enrollment in the first half of 2019 and generate results in early 2021.
GALACTIC-HF is a big cardiovascular outcomes study involving around 8,000 with moderate to severe HFrEF and is intended to show that omecamtiv can extend the time to death or first heart failure event. It is currently around 90% enrolled, according to Amgen.
METEORIC-HF is a much smaller study with a target enrolment of 270 patients and is intended to zero in on one specific symptom of HFrEF, namely loss of exercise capacity. It will look at 20 weeks of treatment with placebo or the cardiac myosin activator on cardiopulmonary exercise testing (CPET), using the same dosing regimen as in GALACTIC-HF.
“Exercise intolerance, typically manifested by shortness of breath and fatigue on exertion, is a predominant symptom of chronic heart failure and often the first symptom that prompts patients to seek medical care,” says Cytokinetics’ head of R&D Fady Malik. “If positive, this clinical trial may provide key clinically relevant evidence.”
The lack of new drug treatment options in heart failure is one reason why survival rates remain stubbornly low and are lagging behind the big improvements seen with other diseases such as cancer.
A recent British Medical Journal study found that one-year survival rates have only crept up between 2000 and 2016, going from 74% to 81%, with Improvement in survival on average 2.4 years greater for patients not requiring admission to hospital around the time of diagnosis.
One advance in drug treatment was the launch of Novartis’ Entresto (valsartan and sacubitril) in 2015, which according to analysts at GlobalData “raised the benchmark” for chronic heart failure therapy”. Initial uptake was slow but it now seems to gathering momentum, with sales breaching the $1bn threshold last year.
The results last year of the PIONEER-HF cardiovascular outcomes trial of Entresto, which showed a is expected to accelerate take-up of the drug in HFrEF.
Amgen, Servier and Cytokinetics are hoping omecamtiv can also make a contribution to improving outcomes in HFrEF. At the moment it seems to be one of the only candidates coming through the late-stage pipeline.