Cost watchdog the National Institute for Health and Care Excellence has turned down Amgen’s Repatha - the world’s first approved PCSK9 inhibitor - as an option for people with high cholesterol and mixed dyslipidaemia.

European regulators approved the drug as a treatment for patients with uncontrolled cholesterol who require additional intensive low-density lipoprotein cholesterol (LDL-C) reduction, after clinical data showed that it induced a reduction in LDL-C of some 55%-75% versus a placebo, and by around 35% to 45% compared with ezetimibe (Merck & Co’s Zetia).

But, in preliminary guidelines out this morning, the Institute said there have been no clinical trials to measure its direct effect on cardiovascular events, and that the question of whether reducing LDL cholesterol with Repatha would reduce angina, heart attacks and strokes “remains unanswered”.

NICE’s review committee also cited several limitations in the company’s analysis. It was concerned that Amgen had estimated the risks of CVD using the Framingham risk equations, “which have been shown to overestimate CVD risk in a UK population, instead of the NICE-recommended and UK-validated QRISK2 assessment tool”, and concluded that “the degree of uncertainty in the cost-effectiveness evidence was too high”.

Repatha’s annual cost per patient comes in at around £4,448.60 for 140mg every two weeks, and £6123.60 for 420 mg monthly, which, given the high number patients that could be eligible for treatment, would represent quite a hefty chunk of NHS resources.

Amgen said it is disappointed by NICE’s decision. “Access to new treatment options for lowering LDL-C in patients who remain at high risk of cardiovascular disease (CVD) is of critical importance,” said Tony Patrikios, executive medical director, Amgen UK & Ireland. “The Department of Health CVD Outcomes Strategy recognises CVD mortality as the largest cause of death in the UK and an area where England underperforms compared to other similar countries. Evidence strongly indicates that high cholesterol is linked to heart attacks and strokes.”

“Amgen will continue to work with NICE to provide further data and analyses to demonstrate the cost-effectiveness of Repatha for relevant groups of patients”.

More than seven million people in the UK are taking statin pills daily, but a significant number report side effects such as joint pain, fatigue, and nausea. According to Amgen, more than 60% of high-risk patients are still unable to adequately lower their bad cholesterol levels despite treatment, underscoring the need for new options.

Consultees, including the company, healthcare professionals and members of the public, now have until December 8 to comment on the preliminary guidance.