Cytokinetics is set to present the benefits of omecamtiv mecarbil – its heart failure drug – to the FDA’s advisory committee. However, the agency appears concerned about the single study used to support the application and whether or not the phase 3 test adequately addressed the company’s requests.
Currently, the drug is being evaluated for its ability to decrease the risk of cardiovascular death and heart failure in patients suffering from chronic heart failure. The application was backed up by the Phase 3 trial known as GALACTIC-HF.
The primary objective of the study was to determine whether or not omecamtiv mecarbil could reduce heart failure events and keep patients out of the hospital; the study met both of these objectives. However, a major secondary endpoint examining cardiovascular death was not achieved, suggesting that the therapy did not prolong patients’ lives.
The FDA has referred several questions about the drug to the Cardiovascular and Renal Drugs Advisory Committee for review, even though this wasn’t the original plan. The FDA initially said it wouldn’t convene the committee despite receiving the application, but later changed its mind.
The committee will meet today to discuss the queries posed by the FDA in its briefing documents. There are many factors to weigh, one of them being whether or not the GALACTIC-HF trial’s findings constitute sufficient proof of efficacy.
During the trial, patients with atrial fibrillation or atrial flutter did not fare better than those given a placebo in terms of heart failure events, and they were at a higher risk of dying from cardiovascular causes. So the committee will also go through the pros and cons of omecamtiv mecarbil in these patients. Lastly, the committee will also mull over whether a dosing strategy based on diagnostic testing is needed for the drug’s safe use.
The FDA explained, “The study showed a statistically significant but small treatment effect on the main endpoint of reducing the events, but the secondary goals were a miss. There were no differences between the arms of the trial for [cardiovascular] death or for all key secondary endpoints that otherwise may have supported the persuasiveness of a single trial.”
Typically, regulatory approval could be obtained with just one trial. But the FDA is of the view that Cytokinetics did not do enough in terms of the secondary endpoints to gain a green light. The treatment effect, according to the agency, had a p-value not good enough for a single trial.
Even if Cytokinetics can persuade the FDA to move past these concerns, it still has other obstacles to deal with concerning omecamtiv mecarbil.
The company had originally proposed a more basic dosing strategy for approval, but this was ultimately scrapped. Under the new strategy, after four weeks of treatment, all patients would be at the maximum dose of 50 mg. However, during the trial, the right dose was determined for patients who might be at a higher risk for overexposure with the aid of diagnostic testing.
Omecamtiv mecarbil has been linked to negative side effects like heart failure and reduced blood flow to the heart. The idea put forth by Cytokinetics might result in excessive exposure and raise the danger of cardiotoxicity, according to the FDA. Cytokinetics ultimately abandoned the new plan as well.