By Alex Keown
Repatha, Amgen’s PSCK9 inhibitor, continues to impress as a treatment for patients with peripheral artery disease (PAD) and a history of heart attacks. New data shows Repatha hit its primary endpoints and significantly reduced first-time cardiovascular events by 27 percent in PAD patients.
In a presentation at the at the American Heart Association Scientific Sessions conference this past weekend, Amgen showed that Repatha (evolocumab) in combination with statins improved clinical outcomes with significant reduction of cardiovascular (CV) events in patients with a history of heart attacks or stroke. Data from Amgen’s Fourier study supports the use of Repatha to reduce the risk of recurrent cardiovascular events in patients with a history of multiple heart attacks. Additionally, the analysis found that Repatha patients who have more recently experienced a heart attack experienced a substantial reduction of a recurring attack.
The Fourier study included 27,564 patients, 3,642 of them had symptomatic PAD. The PAD patients were older and had more CV risk factors, such as hypertension, a history of smoking and diabetes. After being dosed for two-and-a-half years, Repatha patients saw a reduction in LDL from a median of 93 mg to 31 mg.
In its presentation of the Repatha studies, Amgen said the results from the Fourier study highlights Repatha’s ability to reduce the residual risk for CV events particularly in high-risk patients with limited treatment options. One analysis showed the addition of Repatha to statin therapy improved clinical outcomes with significant reduction of CV events in patients with a history of PAD, the company said.
Ransi Somaratne, a former practicing cardiologist who now works with Amgen, said the company was pleased with the results of the trial. Somaratne said the Fourier results once again demonstrate the effectiveness of Repatha as a reducer of LDL. But, he said, the study provided greater information as to how an addition of Repatha can benefit certain subgroups of patients, particularly those with PAD or who have suffered a previous heart attack or stroke.
“The whole group of patients would benefit from LDL reduction, but there are subpopulations that could derive even greater benefits,” Somaratne said in an exclusive interview with BioSpace.
In addition to the subset of patients showcased at the AHA, Somaratne pointed to Repatha’s benefits with diabetes patients as well. In September, the company released data that showed patients with diabetes tended to have a greater absolute risk reduction of cardiovascular events with Repatha treatment due to a heightened risk of cardiovascular morbidity and mortality in patients with atherosclerotic cardiovascular disease.
Somaratne said the benefits of adding Repatha to diabetic patients was similar to PAD patients.
With the new data in hand, Amgen said it is expecting the U.S. Food and Drug Administration to rule on expanding the approved indications for Repatha to include these subsets of patients.
“These are patients for whom an addition of Repatha could provide even more clinical benefit and value,” he said. “The results of the study will further help physicians tailor treatments for their patients who fall into these subsets.”
Repatha was approved by the U.S. Food and Drug Administration in 2015 to treat two rare genetic diseases known for high LDL-C, as well as patients who have atherosclerotic CV disease. Its initial approval was based on clinical evidence that the drug lowered the bad cholesterol by about 60 percent and decreased the rate of cardiovascular events, including heart attack, heart failure leading to hospitalization and death, by approximately 50 percent.
A PCSK9 inhibitor, Repatha binds to PCSK9 and inhibits circulating PCSK9 from binding to the LDL receptor. That prevents PCSK9-mediated LDLR degradation and allows LDLR to recycle back to the liver cell surface. By inhibiting the binding of PCSK9 to LDLR, Repatha increases the number of LDLRs available to clear LDL from the blood, thereby lowering LDL-C levels.
The Fourier study results come about a year after the company showcased Repatha’s benefits in patients with coronary artery disease. The Glagov study showed that Repatha modifies the underlying process of atherosclerosis. Somaratne said the Fourier and Glagov studies have provided Amgen and treating physicians with a lot of information about the benefits of adding Repatha to a treatment regimen.