The FDA update was based on results of the FOURIER trial, which showed the drug reduced the risk of heart attacks, strokes, and revascularizations in high-risk patients.
FDA on Friday approved evolocumab (Repatha, Amgen) as the first PCSK9 inhibitor to prevent heart attacks, strokes, and coronary revascularizations in adults with established cardiovascular disease. Amgen announced the approval in a statement.
The approval is based on results of the FOURIER trial presented in March. The update gives evolocumab an edge over rival alirocumab (Praluent, Sanofi/Regeneron), as sponsors of both proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors work to convince payers their cholesterol-fighting powers are worth a list price of $14,500 a year.
"We are pleased that the FDA made the inclusion of our outcomes data a priority so that patients can benefit from Repatha's ability to reduce life-changing events of heart attacks and strokes," said Sean E. Harper, MD, executive vice president of Research and Development at Amgen. "Despite treatment with current best therapy, many patients are still at high risk for cardiovascular events. Physicians now have a new FDA-approved treatment option to prevent cardiovascular events by dramatically lowering LDL [low-density lipoprotein] cholesterol with Repatha, especially for patients already on maximally-tolerated statin therapy who need further LDL cholesterol lowering."
Evolocumab achieved the new indication through FDA’s priority review process, granted to drugs that treat serious conditions and would offer major improvements in safety or effectiveness over existing options. FDA granted that status in July. Also Friday, FDA approved evolocumab, alongside drugs like statins, to treat patients with primary hyperlipidemia.
When PSCK9 inhibitors were approved in 2015, payers set up strict protocols for allowing access to the drug. It remains to be seen whether Friday’s label change will improve access to evolocumab for patients.
Results in FOURIER, presented at the American College of Cardiology (ACC) Scientific Sessions, showed evolocumab produced a 15% reduction in the combined primary endpoint of heart attack, stroke, unstable angina, coronary revascularization, or cardiovascular death. As noted in Amgen’s statement Friday, these results included the drug’s ability to reduce the risk of heart attack by 27%, the risk of stroke by 21%, and the risk of coronary revascularization by 22%.
Cardiovascular benefits from evolocumab increased after the first year. However, there was no improvement in cardiovascular death, and payers did not share cardiologists’ enthusiasm for the results.
Studies presented at the ACC meeting—and reports from specialists since that time—show that clinicians continue to hit roadblocks when they prescribe PCSK9 inhibitors for patients. “In my experience, it has changed very little. Maybe we have changed a little in terms of our approach to this, possibly some of the payers are little more relaxed,” Eliot A. Brinton, MD, FAHA, FNLA, president of the Utah Lipid Center, told The American Journal of Managed Care® in an interview. With the FOURIER results, he said, “I’m hopeful that this will become less of an issue.”
As FOURIER was released, Amgen offered payers a money-back guarantee if patients had a heart attack while taking the drug. The announcement did trigger some contracting agreements with payers, including an early one with Harvard Pilgrim. But others asked whether the arrangement would yield any real savings. A cost-effectiveness analysis published in JAMA Cardiology earlier this year found that the current list price of $14,523 “exceeds generally accepted cost-effectiveness thresholds,” and that the price would need to fall to $9669 in the United States to achieve the accepted standard of $150,000 per quality-of-life year (QALY). Or, the authors wrote, the drug would need to be targeted to higher-risk populations.
Last month at the American Heart Association Scientific Sessions, additional analyses from FOURIER showed the drug’s effectiveness among 2 groups of very high-risk patients: those with peripheral artery disease, and those with recent or multiple heart attacks and with residual coronary artery disease. Authors of the second study concluded, “These data may permit clinicians to target PCSK9 inhibition to patients who benefit the most.”
Big drops in “bad” cholesterol. A monoclonal antibody, evolocumab works to dramatically reduce low-density lipoprotein or “bad” cholesterol by blocking a protein that prevents the liver from carrying cholesterol out of the body. The injectable drug has been shown in clinical trials to reduce LDL cholesterol as much as 60% when patients take it with metformin.
Evolocumab was approved in August 2015, a month after alirocumab. Both were seen as potential blockbusters, but FDA limited labels for both drugs to patients with 2 forms of familial hypercholesterolemia and to high-risk patients with clinical atherosclerotic cardiovascular disease. FDA said that these high-risk cardiovascular patients must use evolocumab alongside maximally tolerated statins.
Prior to approval, an FDA panel declined to recommend evolocumab for broader groups of patients—including the large number who don’t tolerate statins well—before seeing cardiovascular outcomes results.