THOUSAND OAKS, Calif.—Amgen has submitted a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for evolocumab for the treatment of high cholesterol. The drug candidate is an investigational fully human monoclonal antibody that blocks proprotein convertase subtilisin/kexin type 9 (PCSK9), a protein that hampers the liver’s ability to remove low-density lipoprotein cholesterol (LDL-C), or “bad” cholesterol, from the blood.
“This BLA submission to the FDA marks the first of several submissions to regulatory authorities around the world for our lipid-lowering program and represents a critical milestone in our overall global development program for evolocumab,” Sean E. Harper, M.D., Amgen’s executive vice president of Research and Development, said in a press release. “We look forward to working closely with regulatory authorities to bring this new treatment options to patients with high cholesterol who, despite currently available therapies, are unable to adequately reduce their LDL cholesterol levels.”
The BLA features data from roughly 6,800 patients, including more than 4,500 patients with high cholesterol in 10 Phase 3 trials. Those patients featured individuals with elevated cholesterol on statins with or without other lipid-lowering therapies, individuals who cannot tolerate statins, individuals with heterozygous familial hypercholesterolemia (FH) and individuals with homozygous FH.
FH is an inherited condition that leads to high levels of LDL-C at an early age, and patients can have one of two types of this condition: heterozygous FH, which can cause LDL-C levels that are twice as high as normal, and homozygous FH, which can cause LDL-C levels more than six times as high as normal. The former occurs in approximately one in 200 to 500 people, while the latter appears in only one in a million individuals. Evolocumab received an orphan drug designation for the treatment of homozygous FH last year.
The BLA comes the same day the company announced positive top-line results from its Phase 3 YUKAWA-2 (StudY of LDL-Cholesterol Reduction Using a Monoclonal PCSK9 Antibody in Japanese Patients With Advanced Cardiovascular Risk) study, which sought to evaluate evolocumab in combination with statin therapy in Japanese patients with high cardiovascular risk and high cholesterol. The study met its co-primary endpoints of the percent reduction from baseline in LDL cholesterol at week 12 and the mean percent reduction from baseline in LDL cholesterol at weeks 10 and 12, reporting a percent reduction in LDL cholesterol that was clinically meaningful, statistically significant and consistent with results seen for the same doses in the Phase 2 YUKAWA trial featuring evolocumab compared to placebo.
The YUKAWA-2 trial sought to assess evolocumab’s safety, tolerability and efficacy compared to placebo when combined with statin therapy. Safety was reportedly balanced across the treatment groups; adverse events seen in less than 2 percent of the combination group were nasopharyngitis (colds), gastroenteritis and pharyngitis (sore throat).
Harper noted that Amgen is “encouraged by the evolocumab data from the YUKAWA-2 study in the Japanese patient population and the remarkable consistency we have seen across our clinical program,” adding that “Statins are an important therapy for patients with high cholesterol and adding evolocumab may help lower their LDL cholesterol levels when statins are not sufficient.”
It’s been a busy but positive week for Amgen on this front, since these announcements come a day after the company shared word that the FDA had granted priority review designation for ivabradine for the treatment of chronic heart failure. The drug inhibits the If current in the sinoatrial node, the body’s cardiac pacemaker, and works to slow the heart rate “without negative effects on myocardial contractility or ventricular repolarization,” according to Amgen. Ivabradine gained fast track designation from the FDA in April for patients with chronic heart failure. It was developed by Les Laboratoires Servier and approved by the European Medicines Agency in 2005 for the symptomatic treatment of stable angina and for chronic heart failure in patients with elevated heart rates in 2012. Amgen has the rights to commercialize the drug in the United States thanks to a collaboration with Servier.