Amgen's PCSK9 inhibitor Repatha gains European Commission approval

The European Commission has approved Amgen (US)'s proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor Repatha (evolocumab) for adult patients with primary hypercholesterolaemia, mixed dyslipidaemia, and homozygous familial hypercholesterolaemia (a genetic disorder whereby patients have very high levels of low-density lipoprotein cholesterol [LDL-C] leading to the early onset of cardiovascular disease). Repatha also received an indication for adolescent patients (aged 12 years and over) for the treatment of homozygous familial hypercholesterolemia in combination with lipid-lowering therapies. The decision follows a positive recommendation by the committee for Medicinal Products for Human Use over a month ago (see Europe: 25 May 2015: EU's CHMP recommends approval of eight medicines, including first PCSK9 inhibitor and two PD-1 inhibitors). In combination with statins, and as an adjunct to diet, Repatha has been demonstrated to be effective in enabling patients with uncontrolled cholesterol to reach low-density LDL-C reduction goals. Amgen's marketing focus will be on patient groups unable to control their LDL-C with the maximum tolerated dose of statins (or other lipid-lowering therapies), or in cases where statins are inappropriate due to intolerance or contraindications.

In the Phase II OSLER-1 and Phase III OSLER-2 studies, when administered in combination with standard therapies, Repatha was shown to lower LDL-C by 61% after 11 months of use versus standard therapy alone (see United States - France: 16 March 2015: Amgen, Sanofi, and Regeneron's PCSK9 inhibitors reduce cardiovascular risk in Phase III studies).

Pricing information has not yet been disclosed by Amgen. However, recent media reports suggest that the drug could potentially cost an average of USD3,750 per year within Europe, compared to USD10,000 per year in the US (source: Deutsche Bank). IHS has previously indicated that the cost of a one-year treatment could reach between USD7,000 and USD12,000 per person in the United States. On that basis, sales of Repatha in the European market would initially be worth USD26 million in the first year of sales. A spokesperson for Amgen has been quoted as saying that "our prices are managed with consideration to competition, the local pricing and reimbursement environment and patient-cost sharing obligation, which vary considerably by country". The price differentiation between EU and US markets is typical, and is also influenced by the likelihood that Amgen will face more difficulties from EU regulators than in the US market in proving the cost-effectives of Repatha, as the drug will be compared to the cheaper treatment option of statins (generic statins can cost as little as USD4 per one-month supply). Neither Amgen nor Sanofi/Regeneron (France/US)'s next generation of cholesterol-lowering medication will replace cholesterol-lowering statins such as Lipitor (atorvastatin; Pfizer, US).

The timeline for Repatha's launch in the European Union will interject with an upcoming decision by the US FDA on whether to approve the investigational cardiovascular drug Praulent (alirocumab; Sanofi/Regeneron) which is due on 24 July. The drug is widely expected to be approved. This will be followed by an FDA decision on whether to approve Repatha on 27 August. The market expectation is that both drugs are on the brink of marketing authorisation in the EU and US.

In Europe Sanofi/Regeneron is about two months behind Amgen in securing marketing approval for Praulent; the EU's Committee for Medicinal Products for Human Use (CHMP) is scheduled to meet on 23 July (see here) to consider whether to recommend Praulent for marketing approval in Europe. This recommendation would then have to be given the green-light by the European Commission, a process likely to take about two months. If an approval is confirmed, this would then pave the way for a two-way pricing battle, which could lead to potential price discounts for European payors.

Repatha will be prescribed in Europe at two clinically equivalent dosage levels; 140 mg administered every two weeks or a 420 mg injection administered on a monthly basis. According to a statement by Amgen, for adult and adolescent patients with homozygous familial hypercholesterolaemia, the initial recommended dose is 420 mg once per month. However, in the event this is not sufficient, after 12 weeks of treatment the dose can be increased to 420 mg every two weeks.

Outlook and implications

Repatha and Sanofi/Regeneron's Praluent are expected to become the next cardiovascular blockbusters able to significantly lower low-density lipoprotein cholesterol. From a public health perspective, the new class of medicines holds out the promise of delivering significant new therapy opportunities for patients with poorly controlled hypercholesterolemia. European payors have raised concerns over the potential financial burden of PCSK9 inhibitors, and national regulators are likely to pressure Amgen and Sanofi/Regeneron to compete on discounts, in a bid to reduce costs. Another note of caution that needs to be sounded is that further data is still needed concerning cardiovascular-related outcomes, including heart attacks and strokes, as studies involving a greater number of patients are necessary to evaluate PCSK9 inhibitors' efficacy in reducing cardiovascular events. The FOURIER clinical trial will assess cardiovascular morbidity and mortality for Repatha. Data is not expected before 2017, but could expand the drug's indication for dyslipidaemia patients.

Although Amgen's Repatha has won the race to be the first to launch in Europe, Sanofi/Regeneron are set to gain the advantage of being first-to-market in the larger and more lucrative US market.