THOUSAND OAKS, Calif.—Completing a key step toward filing for regulatory approval of a broadly applicable cholesterol-reducing drug, Amgen has announced promising results from its fifth Phase 3 trial—the RUTHERFORD-2 trial—of evolocumab, a fully human monoclonal antibody inhibiting proprotein convertase subtilisin/kexin type 9 (PCSK9), a protein that reduces the liver’s ability to remove low-density lipoprotein cholesterol (LDL-C) from the blood.
LDL-C is a major risk factor for cardiovascular disease, and more than 71 million Americans have high LDL-C, according to the U.S. Centers for Disease Control and Prevention. Patients who have both high cholesterol and high cardiovascular risk are key target markets for evolocumab.
While the trial’s full results will be announced in Washington, D.C., at the American College of Cardiology’s 63rd Annual Scientific Session in late March, Amgen has said that the drug successfully combined with statins and other lipid-lowering drugs to reduce LDL-C, also called “bad” cholesterol, for patients with heterozygous familial hypercholesterolemia.
Previous trials have found evolocumab useful for patients with high cholesterol who were not previously getting anti-lipid treatment, as well as those already on statin drugs, and those who cannot tolerate statins, the most common type of anti-cholesterol drug.
While statins inhibit an enzyme that controls production of cholesterol in the liver, evolocumab binds to PCSK9, blocking it from binding to LDL receptors on the surface of the liver, according to the company’s description of the drug. That frees up more LDL receptors to remove LDL-C from the blood.
According to the company, a total of 13 trials are slated, including testing varying methods of injecting the drug and different frequencies of administration. About 30,000 patients will be involved, including those with cardiovascular disease, hyperlipidemia, coronary atherosclerosis and familial hypercholesterolemia (whether heterozygous or homozygous).
Those latter conditions, which are genetic, cause high levels of LDL-C starting at birth, and place patients at high risk for cardiovascular problems early in life. Heterozygous familial hypercholesterolemia affects about one in every 300 to 500 people worldwide, according toWorld Health Organization data.
The results so far will be shared with regulators, in hopes of securing approvals in 2014, the company said in a statement to DDNews. The exact timeline depends on results of ongoing trials.
Since Jan. 23, Amgen has touted positive top-line results for evolocumab from the Phase 3 GAUSS-2 trial in statin-intolerant patients with high cholesterol, the Phase 3 LAPLACE-2 trial in combination with statins in patients with high cholesterol and the Phase 3 RUTHERFORD-2 trial in patients with heterozygous familial hypercholesterolemia.
Of the most recently announced top-line results, Dr. Sean E. Harper, executive vice president of research and development at Amgen, said, “Data from the RUTHERFORD-2 study suggest that evolocumab, when used as an add-on therapy to existing lipid-lowering medications, may offer a new treatment option for patients with heterozygous familial hypercholesterolemia. The RUTHERFORD-2 study is the fifth pivotal LDL-C lowering study in our Phase 3 program. The robust data from these five studies will form the basis of our global filing plan, and we look forward to discussions with regulatory agencies.”