The US Food and Drug Administration (FDA) has approved Amgen's cholesterol-lowering medication, Repatha (evolocumab) injection, a human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9), a protein that reduces the liver's ability to remove low-density lipoprotein cholesterol (LDL-C), or bad cholesterol, from the blood.
Repatha is indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease (ASCVD), who require additional lowering of LDL-C; and as an adjunct to diet and other LDL-lowering therapies for the treatment of patients with homozygous familial hypercholesterolemia (HoFH), who require additional lowering of LDL-C. The effect of Repatha on cardiovascular morbidity and mortality has not been determined.
"We are excited about today's approval of Repatha in the US as patients and physicians will now have a new treatment option to lower LDL cholesterol," said Sean E. Harper, M.D., executive vice president of research and development at Amgen.
"Data from key clinical studies have shown that Repatha significantly reduces LDL cholesterol in patients who have not been able to lower their LDL cholesterol through diet and statins alone. At Amgen, we are committed to improving the lives of patients and are inspired by the potential for Repatha to aid in the global fight against one of the major risk factors for cardiovascular disease."
Elevated LDL-C is an abnormality of cholesterol and/or fats in the blood. In the US, there are approximately 11 million people with ASCVD and/or familial hypercholesterolemia (FH), who have uncontrolled levels of LDL-C over 70 mg/dL, despite treatment with statins or other cholesterol-lowering therapies. Familial hypercholesterolemia is caused by genetic mutations that lead to high levels of LDL-C at an early age. It is estimated that one million people in the US have FH (heterozygous and homozygous forms), yet less than one percent are diagnosed.7
"Through PCSK9 inhibition, evolocumab substantially reduces LDL or bad cholesterol, a well-validated, modifiable risk factor for cardiovascular disease," said Marc Sabatine, M.D., M.P.H., chairman of the TIMI Study Group, the Lewis Dexter, MD distinguished chair in cardiovascular medicine at Brigham and Women's Hospital, and professor of medicine, Harvard Medical School, Boston.
"Many patients still require further LDL cholesterol lowering and evolocumab now offers an important new treatment option for them."
In phase 3 trials, adding Repatha to background lipid-lowering therapy that included statins resulted in intensive reductions in LDL-C levels with favourable effects on other lipid parameters. In patients with clinical ASCVD or HeFH, Repatha reduced LDL-C by approximately 54 to 77 per cent compared with placebo. In a pivotal phase 3 trial, 90 per cent of clinical ASCVD patients who received Repatha in addition to maximum doses of statins achieved a LDL-C level less than 70 mg/dL. In patients with HoFH, Repatha reduced LDL-C by approximately 30 per cent compared with placebo.
Repatha is generally well-tolerated with an established safety profile. The most common adverse reactions that occurred in greater than 5 per cent of the Repatha group, and more frequently than in the placebo group, were nasopharyngitis, upper respiratory tract infection, influenza, back pain and injection site reactions.
Repatha is available as a single-use 140 mg prefilled SureClick autoinjector or prefilled syringe that patients can self-administer at the recommended dose for adults of 140 mg every two weeks or 420 mg once a month. For adults with HoFH, the recommended dose is 420 mg once a month. Amgen will continue discussions with the FDA regarding the 420 mg every two weeks dosing for HoFH patients.
The US Wholesale Acquisition Cost (WAC) price of Repatha is $542.31 for one 140 mg single-use prefilled SureClick autoinjector or prefilled syringe, or $14,100 annually for the every two weeks administration. For the monthly 420 mg administration, Amgen plans to make a single injection monthly dosing option available next year. Until then, Amgen anticipates monthly administration predominately for HoFH patients. Actual costs to patients, payers and health systems are anticipated to be lower as WAC pricing does not reflect discounts or rebates. Out-of-pocket costs to patients will vary depending on insurance status and eligibility for patient assistance.
"Amgen is sensitive to the concerns of payers around cost, budget predictability and paying for value," said Anthony C. Hooper, executive vice president of global commercial operations at Amgen. "We are confident in the ability of Repatha to demonstrate real-world effectiveness and value based on intensive LDL cholesterol reductions, and we will be working with payers and other purchasers to provide innovative pricing programmes linking the net price of Repatha to the expected LDL cholesterol reductions and anticipated appropriate patient utilisation. By partnering with payers to implement these programmes, we can help ensure that all appropriate patients who could benefit from Repatha will have access to this important new therapy."
Amgen is committed to providing personalized support services for patients and providers in the U.S. through its RepathaReady programme. RepathaReady is a comprehensive suite of services to help patients and providers, including one or more months of free Repatha through the Repatha Patient Start Programme while insurance coverage is pending; the Repatha $5 co-pay card for eligible commercial patients; insurance coverage support; and injection training.
Amgen also provides patient assistance for its medicines marketed in the US in a variety of ways, including free medicines through The Safety Net Foundation for qualifying individuals with no or limited drug coverage.
Repatha is expected to be available in the US next week. The US approval of Repatha follows the marketing authorisation of Repatha in Europe, which was announced on July 21, 2015.
GLAGOV, the intravascular ultrasound study, is underway to determine the effect of Repatha on coronary atherosclerosis in approximately 950 patients undergoing cardiac catheterization to test the hypothesis of robust LDL-C reduction leading to a reduction or a change in the build-up of plaque in the arteries. Results from the GLAGOV study are expected in 2016.
The FOURIER outcomes trial is designed to evaluate whether treatment with Repatha in combination with statin therapy compared to placebo plus statin therapy reduces the risk of recurrent cardiovascular events in patients with high cholesterol and clinically evident cardiovascular disease and completed patient enrollment in June 2015. Results from the approximately 27,500-patient FOURIER study are expected no later than 2017 (event-driven).