NICE: Inclisiran for Treating Primary Hypercholesterolaemia or Mixed Dyslipidaemia

Dawn O'Shea

October 11, 2021

National Institute for Health and Care Excellence (NICE) has issued new guidance which recommends inclisiran as an option for treating primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia as an adjunct to diet in adults.

The treatment is recommended only if:

  • There is a history of any of the following cardiovascular events:

  • LDL-cholesterol (LDL-C) concentrations are persistently ≥2.6 mmol/L, despite maximum tolerated lipid‑lowering therapy, which is defined as maximum tolerated statins with or without other lipid-lowering therapies or other lipid-lowering therapies when statins are not tolerated or are contraindicated.

Clinical trial evidence has shown that inclisiran can lower LDL-C levels when statins or other lipid-lowering therapies have been unsuccessful in meeting targets; however, there are no data directly comparing inclisiran with ezetimibe, alirocumab or evolocumab. There is also no long-term evidence on whether inclisiran reduces cardiovascular events. As a result, there is considerable uncertainty about the trial results and, consequently, about cost-effectiveness estimates.

Despite these uncertainties, a NICE appraisal committee concluded that inclisiran is still cost effective in people who have previously had a cardiovascular event and have persistently high LDL-C levels despite maximum lipid-lowering therapy.

For patients with primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia who do not have a history of cardiovascular events, cost-effectiveness estimates were very uncertain, and the committee estimated that the cost was likely to be above the threshold that NICE considers an acceptable use of NHS resources. Hence, in this population, the treatment is only recommended for use in the research setting. A clinical trial is currently in development to examine inclisiran’s effect on cardiovascular events in this population.

It is expected that inclisiran would be given by a primary care professional. After an initial dose, it would be given again after three months and then twice a year. This will represent a change from the current situation where available treatments, such as alirocumab and evolocumab, are usually prescribed in secondary care.

NICE said it has been made aware of some concerns surrounding the implementation of inclisiran in a primary care setting but noted that the Accelerated Access Collaborative and NHS England had plans to support this implementation. The ongoing implementation research project (SPIRIT) is also aiming to assess the feasibility of delivering inclisiran within a primary care setting in England. This trial is due to complete in 2022 and is expected to provide information on how the treatment can be delivered in primary care.

The appraisal committee strongly recommended that this guidance should be reviewed once more mature cardiovascular outcome data are available. This would validate whether LDL-C reduction is an appropriate surrogate outcome for inclisiran.

A randomised controlled trial (ORION-17) of the effectiveness of inclisiran compared with placebo in the primary prevention of cardiovascular disease is being developed.

The ongoing ORION-4 trial of the use of inclisiran for primary prevention is due to conclude in 2026. An additional global trial of a similar design was in development.

An ongoing trial is also aiming to compare inclisiran and lipid-lowering medication with or without behavioural support and lipid-lowering medication without inclisiran with behavioural support (SPIRIT). This trial will also assess the feasibility of delivering the treatment within a primary care setting in England and is due to be completed in 2022. 

This article originally appeared on Univadis, part of the Medscape Professional Network.

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