Following European Commission (EC) authorisation,1 Sanofi has announced that a new medicine, Praluent (alirocumab), is now available for certain adult patients with hypercholesterolaemia in the UK.
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.2 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.2
Dr Adie Viljoen, UK Chief Investigator of three clinical studies involving alirocumab and Consultant Chemical Pathologist, Lister Hospital, Hertfordshire said: "Alirocumab will provide high risk patients with HeFH and those with high CV risk who have not responded adequately to optimal lipid lowering intervention including life style modification and treatment with high intensity statins, a new option to reduce their cholesterol levels with the aim of reducing their risk of heart attack and stroke."
High cholesterol levels represent a major risk factor for cardiovascular disease (CVD).3 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.4 Only twenty-four percent of high risk patients, such as those who have already had a heart attack and who are on statin monotherapy, achieve their optimal LDL cholesterol goal of 5 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.6
Alirocumab is a PCSK9 (proprotein convertase subtilisin kexin type 9) inhibitor2 that was jointly developed by Sanofi and Regeneron Pharmaceuticals. PCSK9 is a naturally occurring protein that prevents the liver from clearing LDL cholesterol out of the blood.7,8,9 Alirocumab works by blocking the action of PCSK9, thereby allowing the liver to clear more LDL cholesterol from the blood, and so reducing LDL cholesterol levels.2
Alirocumab is the only PCSK9 inhibitor with the flexibility of being available in two different starting strengths (75 mg and 150 mg) to be used once every two weeks as a single 1-millilitre (ml) injection.2
"The discovery of PCSK9 was a significant advance in the understanding of LDL cholesterol lowering," said Dr. David Williams, Medical Director, Sanofi UK. "The availability of alirocumab represents a real breakthrough for those adult patients with high cardiovascular risks whose needs are not being met by older cholesterol-lowering therapies. Sanofi is committed to working with the medical community to help these patients to achieve their LDL cholesterol goals."
The marketing authorisation of Praluent is based on data from 10 pivotal Phase 3 ODYSSEY trials. Results showed consistent reductions in LDL (or 'bad') cholesterol for alirocumab compared to placebo or ezetimibe, when added to current standard-of-care.2
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, significantly more patients achieved an LDL-cholesterol level of less than 70 mg/dL 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.2
About the ODYSSEY trials
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 8.2 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 initially started on alirocumab 150 mg every two weeks, the average LDL cholesterol 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 trial.2
Local injection site reactions including erythema/redness, itching, swelling or pain/tenderness were common events in 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.2
In July, alirocumab was licensed for use in the U.S., in addition to diet and maximally-tolerated statin therapy, for the treatment of adults with HeFH or clinical atherosclerotic CVD, who require additional lowering of LDL-cholesterol.10
The effect of alirocumab on CV morbidity and mortality has not yet been determined.2