Praluent approved by NICE for people with raised cholesterol levels who are at significantly high risk of a heart attack or stroke

Praluent® has been shown to reduce 'bad' cholesterol by 61% in a clinical trial.¹

Sanofi has announced that the National Institute for Health and Care Excellence (NICE) has recommended Praluent® (alirocumab) as a treatment option for people who have raised levels of 'bad' cholesterol (low-density lipoprotein cholesterol), or LDL-C, and who are at significantly high risk of a heart attack or stroke.^{2, 3}

Sanofi welcomes NICE's decision at the Final Appraisal Determination (FAD) phase to recommend alirocumab as a treatment option for certain people with inherited raised cholesterol levels and those at high risk of cardiovascular events.² Praluent is authorised for use in patients who are unable to reach their low-density lipoprotein (LDL), or 'bad' cholesterol treatment goals, despite modifying their diet and taking a maximum tolerated dose of a statin and/or other lipid-lowering therapies.³ These patients include those with: high levels of LDL cholesterol; an inherited form of high cholesterol levels - heterozygous familial hypercholesterolaemia (HeFH); and patients who are statin intolerant, or contraindicated.³ The effect of alirocumab on CV morbidity and mortality has not yet been determined. The product was developed jointly by Sanofi and Regeneron.

"Praluent represents an important innovation in the therapeutic options available to treat people living with raised cholesterol levels. Sanofi is pleased with today's positive recommendation from NICE as it will allow healthcare professionals to better manage their patients at a significant level of risk of cardiovascular disease." said Dr Tunde Falode, Director of the Cardiovascular Division at Sanofi. "Importantly, Praluent is the only PCSK9 inhibitor available in two different strengths - 75 mg and 150 mg - providing doctors with the flexibility to meet the needs of their individual patients."

Alirocumab belongs to the most recent cholesterol-lowering class of treatments called PCSK9 inhibitors. PCSK9 is a protein that plays an important role in managing 'bad' cholesterol by regulating the number of receptors for 'bad' cholesterol on the liver's surface. By reducing PCSK9, the treatment increases the availability of receptors for 'bad' cholesterol and therefore lowers the levels of 'bad' cholesterol in the blood.³

Despite the widespread use of statins and other lipid-lowering therapies to reduce raised cholesterol levels, some people in the UK remain at significant risk of having a cardiovascular event and are unable to lower their cholesterol to levels indicated within national guidelines.⁴ In the ODYSSEY LONG TERM clinical trial where people with raised cholesterol levels and at high risk of developing a cardiovascular event were treated with alirocumab 150 mg every two weeks, alirocumab was able to reduce 'bad' cholesterol by 61% at week 24 versus an increase of 0.8% for the patients on placebo.¹ In this trial, patients in both treatment groups were also receiving statins at the maximum tolerated dose.

"This recommendation includes several groups of patients, all of whom need to have their LDL-cholesterol (bad cholesterol) reduced and now a larger number of patients will potentially benefit from these treatments." Said Dr Adie Viljoen, UK Chief Investigator of three clinical studies involving alirocumab and Consultant Chemical Pathologist, Lister Hospital, Hertfordshire. "We now have an approved new medication available to improve the treatment of uncontrolled high cholesterol".

Raised cholesterol levels continue to represent a major risk factor for cardiovascular disease (CVD).⁵ Each year, CVD accounts for a quarter of all deaths in the UK: that's approximately 155,000 people or one person dying every three minutes.⁶ A European study of over 7,000 patients showed that significant numbers of high risk and very high risk patients (60% - 80% respectively) were unable to adequately lower their 'bad' cholesterol levels with statins or other lipid-lowering therapies.⁷ Familial Hypercholesterolemia (FH) is an inherited disorder which causes people to have cholesterol levels which are higher than normal from birth. The prevalence of FH in the UK population is estimated to be 1 in 500,⁸ however an estimated 85% of people living with FH remain undiagnosed.⁹ Without treatment, people with FH can die prematurely of heart disease in their 20s, 30s and 40s.⁸

Furthermore, although CVD death rates have fallen, healthcare costs to the NHS in England have risen from £6,940 million to £7,880 million between 2003 and 2010 due to an increase in the costs associated with managing these conditions.⁴

As part of its submission to NICE, Sanofi offered an upfront patient access scheme, which includes a confidential discount to the NHS, as a sign of its commitment to seeing patients in the UK benefit from this treatment.

About the ODYSSEY Trials³

The clinical evidence for the efficacy of alirocumab is supported by an extensive clinical development programme (ODYSSEY), involving over 5,000 patients with raised cholesterol levels worldwide.

The marketing authorisation of alirocumab is based on data from 10 pivotal Phase 3 ODYSSEY trials. Results showed consistent reductions in LDL-cholesterol (or 'bad') for alirocumab compared to placebo or ezetimibe, when added to current standard-of-care which included statins at the maximum tolerated dose.

All trials met their primary efficacy endpoint, demonstrating significantly greater reductions from baseline in LDL-cholesterol at week 24, compared to placebo or ezetimibe. In addition, a significantly higher proportion of patients achieved an LDL-cholesterol level of less than 70 mg/dL (1.81 mmol/L) in the alirocumab group compared to placebo or ezetimibe at week 12 and week 24. Both the 75 mg and 150 mg alirocumab doses will be available via a pre-filled pen.

In the Phase 3 ODYSSEY trials, patients who initially started on alirocumab 75 mg every two weeks experienced average LDL-cholesterol reductions from baseline ranging from 43.6 percent to 51.2 percent at week 12. In these trials, patients initially started on alirocumab 75 mg every two weeks. These patients had their dose uptitrated to 150 mg every two weeks at week 12 if additional cholesterol-lowering was required, based on pre-specified criteria at week 8. In the trials with this up-titration regimen, the majority of patients achieved their pre-defined LDL-cholesterol target on the 75 mg dose, and maintained treatment at this dose.

In the trials where patients started on alirocumab 150 mg every two weeks, the LDL-C reductions from baseline ranged from 46.9 to 63.3 percent, at week 12. In ODYSSEY LONG TERM trial, efficacy was sustained throughout 78 weeks of the study.

Local injection site reactions including erythema/redness, itching, swelling or pain/tenderness were common adverse events in the clinical trials (6 percent with alirocumab versus 4 percent with placebo). Most injection site reactions were transient and of mild intensity. Other common adverse events included upper respiratory tract signs and symptoms, and pruritus. The observed cases of pruritus were typically mild and transient.