A new way to lower so-called "bad cholesterol" (LDL-C) is now available in the UK - the first in a new class of treatment to help people who are unable to get below guideline cholesterol levels using existing medicines and an appropriate diet. Using a fortnightly injection of Repatha® (evolocumab) on top of statin treatment (80mg atorvastatin), patients in one clinical trial achieved an average LDL-C reduction that was 75% lower than those taking atorvastatin alongside a placebo (mean LDL-C, weeks 10-12)2. It can also be taken on its own by people who are unable to take a statin1.
Evidence has shown that high cholesterol increases the risk of atherosclerosis, heart attack and stroke3. Coronary Heart Disease (CHD), which leads to angina and heart attacks, remains the leading cause of death in the UK4.
Although a healthy diet and taking statins can be effective in reducing excessively high cholesterol (hypercholesterolaemia) to less risky levels, current options alone are unsuccessful for a significant number of people. Researchers have found that approximately 45 per cent of patients at high risk for cardiovascular disease (CVD) do not adequately lower their LDL-C levels with statins and/or other currently licensed lipid-lowering agents to achieve therapeutic goals5.
The science behind evolocumab is based on genetic insights into people who have especially high6, and especially low7, levels of a protein called PCSK9 - which inhibits the body's natural system for eliminating LDL-C from the blood. Evolocumab is a human monoclonal antibody that blocks PCSK9.
"Statins transformed our management of raised cholesterol and our understanding of this key risk factor for strokes and heart attacks," said Dr Terry McCormack, Principal in General Practice in Whitby, Secretary of the British Hypertension Society and evolocumab clinical trial investigator. "But our best efforts with statins - which remain the front line of therapy alongside low-fat diets, exercise and smoking cessation - still leave a significant number of patients with inadequately controlled cholesterol levels."
One condition linked to persistently raised cholesterol is familial hypercholesterolaemia (FH). It is one of the most common life-threatening genetic diseases8, affecting between 1 in 500 and 1 in 200 people (0.2 - 0.5 per cent)9,10. Those carrying FH genes experience persistently raised LDL-C. In a recent multi-centre study of almost 5,000 patients across Europe, possible FH (defined according to the UK Simon Broome criteria) was found in 5 per cent of people suffering a heart attack (Acute Coronary Syndromes, ACS) and 14 per cent of people having a heart attack at a young age.11 Even among patients attending specialist clinics, a national audit found that only 44 per cent of adult patients achieved the recommended target of 50 per cent reduction in LDL-C from the untreated level12 - as recommended in NICE guidelines.9 Treatment of FH patients is included in the recently published Summary of Product Characteristics (SmPC) for evolocumab1.
"Today's announcement will be welcomed by our high risk patients and their families," said Dr Dermot Neely, who runs the specialist Lipid Clinic at the Royal Victoria Infirmary (RVI) in Newcastle and is a HEART UK trustee13. "It is over a decade since the last new drug class for cholesterol lowering therapy was introduced in the UK. We now have a new treatment option which may be considered in patients who are resistant to statins or unable to take them. In particular, our patients with severe forms of FH frequently have persistently raised cholesterol levels and remain at serious risk of having a heart attack or stroke, despite a healthy diet, healthy lifestyle and currently available lipid-lowering treatments in maximum combinations."
In clinical studies1, LDL-C reductions of 55 to 75 per cent were achieved versus placebo as early as the first week of treatment and maintained during long-term therapy. Based on either a 140mg self-administered injection every 2 weeks, or 3 such injections (420mg) once a month, evolocumab demonstrated a reduction in LDL-C of more than half in 80 to 85 per cent of patients.
Across studies of more than 6,000 patients with raised LDL-C, the most commonly reported adverse reactions were nasopharyngitis (4.8 per cent), upper respiratory tract infection (URTI, 3.2 per cent), back pain (3.1 per cent), influenza (2.3 per cent), arthralgia (2.2 per cent) and nausea (2.1 per cent).
John Kearney, General Manager, Amgen UK & Ireland, said: "We deeply appreciate the commitment of the patients and health professionals who have participated in clinical trials in the UK and made today's announcement possible. We will now work eagerly with all our partners and stakeholders in the NHS to see how this medicine can begin to help UK patients."
The effect of evolocumab on cardiovascular morbidity and mortality has not yet been determined1. An ongoing study, FOURIER, is exploring the extent to which the LDL-C reductions achieved by evolocumab treatment may prevent future cardiovascular events such as heart attacks and strokes. From a total of 27,564 patients enrolled globally in the trial there are 1,490 in the UK; spread across 79 trial centres nationwide. The study results are expected in 2017.
Amgen is working with the National Institute for Health and Care Excellence (NICE) in its review of the use of evolocumab for the treatment of primary hypercholesterolaemia and mixed dyslipidaemia. This NICE review is in progress and is expected to publish guidance for the NHS on use of evolocumab in April 2016.