European Commission grants licence for inclisiran (Leqvio® ▼), a first-in-class siRNA cholesterol-lowering treatment

• Cardiovascular disease (CVD) causes more than a quarter of all deaths in the UK; claiming nearly 170,000 lives each year.¹

• Inclisiran is the first and only small interfering RNA (siRNA) to treat primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia,² two common forms of elevated cholesterol linked to increased risk of cardiovascular disease.^3,4 The medicine is indicated in these patient populations as an adjunct to diet, in combination with a statin, or statin with other lipid-lowering therapies for those not reaching their low-density lipoprotein (LDL) cholesterol target with the maximum tolerated dose of a statin, or alone or in combination with other lipid-lowering therapies in patients who are statin-intolerant or for whom a statin is contraindicated.²

• The licence follows the announcement in early 2020 that the UK will pioneer an innovative population health model, expected to make inclisiran available through a population-level agreement in a first of its kind approach to reducing the risk of heart disease.^5,6

London, UK. 11 Dec 2020 Novartis today announced that the European Commission (EC) has granted a licence for the use of inclisiran (Leqvio^®▼) for the treatment of adults with primary hypercholesterolemia (heterozygous familial and non-familial) or mixed dyslipidaemia,² two common forms of elevated cholesterol.^3,4 The medicine is indicated in these patient populations as an adjunct to diet, in combination with a statin, or statin with other lipid-lowering therapies for those not reaching their low-density lipoprotein (LDL) cholesterol  target with the maximum tolerated dose of a statin, or alone or in combination with other lipid-lowering therapies in patients who are statin-intolerant or for whom a statin is contraindicated.²

Inclisiran is a first-in-class, small interfering RNA (siRNA) cholesterol-lowering treatment administered as a single injection initially, at 3 months and then at 6-month intervals. Using a novel mechanism of action, the treatment has been shown to deliver effective and sustained LDL cholesterol reduction in patients with atherosclerotic cardiovascular disease (ASCVD).^2,9,10

Following the granting of this marketing authorisation by the EC - and pending further approval from the National Institute for Health and Care Excellence (NICE) - Novartis and the NHS will continue pioneering an innovative population health model announced earlier this year, which is expected to make the medicine available through a population-level agreement in a first of its kind approach to reducing the risk of heart disease. This collaboration also includes the creation of an industry and academic consortium to improve the efficiency in which the UK can manufacture this form of treatment.^5,6

In the UK, heart and circulatory diseases cause more than a quarter (27%) of all deaths each year, and 7.4 million people are living with these diseases every day.¹ The NHS has recognised cardiovascular disease as a clinical priority, identifying this as the single biggest area in which lives can be saved over the next ten years, and made a long-term commitment to prevent over 150,000 heart attacks, strokes and dementia cases, over the next ten years.⁷

Commenting on the benefits of providing a cholesterol-lowering population health approach to tackling cardiovascular disease at the primary care level, Dr Tracey J. Vell MBE, GP for the Manchester Local Medical Committee, said: “In the area of cholesterol management, Health Innovation Manchester and the Greater Manchester system have been delighted to apply a population health management methodology to the implementation of this new medicine. It allows us to identify at risk groups digitally, and then deliver innovative long acting cholesterol lowering therapy alongside other holistic care objectives. Through this we are hoping to deliver better outcomes for those at risk of cardiovascular disease as well as care close to their home and community.”  

Patients with established ASCVD are increasingly falling short of achieving and maintaining guideline-recommended LDL cholesterol goals, leaving them at high cardiovascular risk.⁸ This highlights the current need for greater utilisation of non-statin LDL cholesterol–lowering therapies, particularly for patients at highest CVD risk.⁸

“Inclisiran has shown considerable and significant improvements in the reduction of cholesterol levels, which could really help in our ongoing battle to tackle the growing burden of cardiovascular disease in the UK. This new treatment, with a novel mechanism of action, could also help address two major barriers to improving population health. Namely, achieving even lower cholesterol levels for those most at risk, above that of maximally tolerated statins, and the challenge of long term non-adherence commonly encountered with current treatments, which require frequent dosing.” said Professor Kausik Ray, Prof of Public Health, Imperial College London and Honorary Consultant Cardiologist at the Imperial College NHS Trust.

“There is a real and pressing need for new, innovative treatments that can help people manage high cholesterol levels – alongside other medication, healthy eating and lifestyle changes – to prevent the associated risks of cardiovascular disease. HEART UK welcomes this authorisation which marks a big step forward in our ability to help people prevent heart disease, heart attacks and stroke in the UK.” comments Jules Payne, Chief Executive at cholesterol charity HEART UK.

“At Novartis, our purpose is to reimagine medicine. I am proud to say that inclisiran, thanks to this licence, could now be part of this journey. As the first and only treatment of its kind, inclisiran embodies our commitment to develop innovative therapies that expand the frontiers of cardiovascular medicine. I am confident that our pioneering and ongoing collaboration with NHS England could help ensure the benefits of this innovation can truly be realised for hundreds of thousands of patients across the UK.” said Chinmay Bhatt, Managing Director UK, Ireland & Nordics for Novartis Pharmaceuticals.

The granting of marketing authorisation by the EC was based on results from the Novartis ORION clinical research programme, including phase 3 trials ORION-9, ORION-10 and ORION-11, which involved over 3,600 patients and assessed the safety, efficacy and tolerability of inclisiran.^9,10

In ORION-9, significant reductions in LDL cholesterol levels were seen in patients with all genotypes of heterozygous familial hypercholesterolemia, who were already taking a maximally tolerated statin dose.⁹ In ORION-10 and ORION-11, patients with ASCVD (& at risk equivalents in ORION-11) who were already taking a maximally tolerated statin dose, achieved ≥50% reduction in mean placebo-adjusted LDL cholesterol at month 17. A time-averaged LDL cholesterol reduction of 52% and 49% respectively, was observed from month 3 to 18, vs. placebo.¹⁰ Across these trials, the safety profile between the inclisiran and placebo groups were similar, apart from injection-site adverse events being more common within the inclisiran treatment group, with the events graded as mild or moderate, with none being severe or persistent.^9,10

Following granting of this marketing authorisation by the EC, Novartis is continuing to work with relevant stakeholders within health agencies to ensure implementation can be provided to secondary prevention ASCVD patients, subject to further NICE approval.