The Food and Drug Administration on Tuesday rejected a closely watched treatment for a form of heart failure amid concerns the drug’s modest benefits don't outweigh its risks to patients.
Cytokinetics, the drug’s developer, said the FDA judged the available clinical trial evidence to be “not sufficiently persuasive,” and asked for data from an additional study. The South San Francisco-based biotechnology company does not currently plan to run that trial, it said in a Tuesday statement announcing the rejection.
The FDA’s decision comes two months after an outside advisory panel voted against the drug, called omecamtiv mecarbil, due to its relatively small treatment effect, lack of a mortality benefit and questions about its safety.
“We are disappointed with this outcome, especially considering the high unmet need for innovative treatments for patients suffering from worsening heart failure,” said Robert Blum, Cytokinetics’ CEO, adding in the company’s statement that it will engage with the FDA to consider next steps for the drug.
Cytokinetics began research and development of omecamtiv mecarbil 15 years ago, originally joined by Amgen, but the larger drugmaker ended the collaboration after disappointing Phase 3 results in 2020.
The twice-a-day pill is meant to treat a type of heart failure in which the left ventricle is weakened and pumps out less blood, commonly referred to as reduced ejection fraction. The study, dubbed GALACTIC-HF, met its primary goal and showed the drug lowered the risk of cardiovascular death or other heart events by 8%, below Amgen’s target of 15%.
Because the trial enrolled more than 8,000 participants, Cytokinetics had argued its size made analysis of subgroups more meaningful, and pointed to a 15% reduction in risks for the sickest patients. At the December advisory meeting, it recommend the drug be approved only for use in patients who are likely to benefit the most.
In briefing documents released ahead of that meeting, FDA staff raised questions about the drug’s dosing and risks to some groups of patients like those with atrial fibrillation and atrial flutter. The heart, like any muscle, needs its function kept within a certain range. To do that with omecamtiv mecarbil, patient blood levels were monitored in clinical testing using a specialized test to avoid exceeding levels associated with higher risk.
Cytokinetics proposed at the December meeting a simpler protocol for stepping up patients’ dosage and switching to another monitoring test.
Typically, heart failure is treated with diuretics and blood pressure medicines. For the subset of patients with reduced ejection fraction, a number of newer drugs have been approved in recent years like AstraZeneca's Farxiga, Boehringer Ingelheim’s Jardiance, and Merck & Co. and Bayer's Verquvo.
While omecamtiv mecarbil’s rejection isn’t a surprise after the advisory panel vote, what has been is investors’ optimism — the company’s stock has traded higher since that meeting. At the time, Mizuho analyst Salim Syed said a negative vote was viewed by some investors as a positive because it could lead Cytokinetics to reduce its spending and focus on its other drug, known as aficamten.
That drug is designed to treat obstructive hypertrophic cardiomyopathy, or HCM, a condition in which the heart muscle thickens and impairs its ability to pump blood. Phase 3 data are expected for the drug in HCM by the end of the year, and if positive, could position it similarly to a MyoKardia medicine that Bristol Myers Squibb bought in a $13 billion acquisition.
“Frankly, many of our investors are more interested in [HCM] than heart failure just given that it's an area that is emerging as a stronger economic opportunity for us,” Fady Malik, head of R&D for Cytokinetics, in an interview ahead of the FDA decision.
Bristol Myers won FDA approval of MyoKardia’s drug, now branded as Camzyos, for obstructive HCM in April 2022, and it went on to generate $24 million in sales for the rest of the year. Bristol Myers forecast Camzyos reaching $4 billion in sales by 2029.