The heart drug met primary endpoint but failed to make the ultimate impact needed.
Cytokinetics’ stocks plummeted Thursday after they released topline results from their Phase III cardiovascular clinical trial with partners Amgen and Servier. While primary endpoints were met, the secondary endpoint to prove potential to save lives failed.
The trial, GALACTIC-HF, was intended to show that treatment with their cardiac myosin activator, omecamtiv mecarbil, would drastically improve odds for heart failure patients with reduced ejection fraction (HFrEF). The 8,256 person study did show a significant 8% reduction in the odds of hospitalization or other urgent care visits for heart failure. But it failed in the key marker – helping high risk patients live longer.
“Trial technically worked,” Mizuho’s Salim Syed wrote to investors, “but failed on what was really needed here to be a foundational medicine, in my view, which is CV death.”
In patients with HFrEF, the muscle of their left ventricle is not contracting enough to squeeze out the amount of blood it should to supply the body. The drug on trial is intended to activate myosin, the motor protein with a strong role in muscle contraction, to help the heart contract and pump as it should.
The trial had incredibly high hopes after a similar product by MyoKardia delivered big on its Phase III trial ending in May. MyoKardia’s drug, mavacamten, also targeted myosin but in the opposite way, by inhibiting it to treat obstructive hypertrophic cardiomyopathy, where the heart is contracting too vigorously leading to obstructed blood flow. In fact, the trial went so well that Bristol Myers Squibb announced this week that it is buying MyoKardia for a cool $13.1 billion by the end of the year.
After MyoKardia’s success, the failure of GALACTIC-HF to meet its secondary endpoint of extending life expectancy was a tough blow. Heart failure is the leading cause of hospitalization in people 65 and older. Nearly 5 million Americans are currently living with heart failure and more than half of those diagnosed will die within 5 years of diagnosis. Approximately 550,000 new cases are diagnosed each year.
However, there is always something to be learned when expectations for a trial are not met. David M. Reese, M.D., executive vice president of R&D at Amgen promised to keep his hand to the plow and said, “The outcomes observed in GALACTIC-HF further the understanding of treating heart failure. At Amgen, we remain committed to developing and delivering transformative medicines that improve the lives of patients with cardiovascular disease.”
This trial was one of the largest heart failure trials ever conducted and will provide valuable insight into the effects associated with targeting cardiac muscle contractility. The full results will be presented after further analyses at the American Heart Association Scientific Sessions 2020.
An additional trial for the same drug is currently in process to assess its effect on exercise capacity in subjects with HFrEF. The study began in April 2019 and is expected to be completed by November 2021.
