RCGP and BMA update: Information on the proposals for the prescription of inclisiran in primary care settings

The RCGP and BMA have discussed the proposed roll out of inclisiran within primary care with NHS England and Improvement following concerns raised by our members and then subsequently a BMJ editorial asking for the drugs approval to be reconsidered.1

This webpage was published on 2 December 2021
Updated 7 July 2022

Background

Inclisiran is a new and novel medication designed to reduce the level of LDL-cholesterol in the blood and works by inhibiting the production of PCSK9 in the liver. It differs from other PCSK9 inhibitors in that it has an intracellular method of action preventing the translation of the PCSK9 protein, whereas others (e.g. alirocumab and evolocumab) bind to and inhibit the protein directly. It is given by injection at 0, 3 and 6 months and then twice a year for life.2

In England, NICE has determined it is cost effective for secondary prevention (as long as the current funding agreement continues) in patients who have a history of cardiovascular events and a persistent LDL-C level of 2.6mmol/l or more, despite maximum tolerated lipid lowering therapies.3 In Scotland, the threshold is higher, requiring an LDL-C of 3.5mmol/l before prescribing in this group and is only approved for use in secondary care. In England, NICE suggests the drug may be administered in a primary care setting.4

The SPIRIT implementation research project, sponsored by Novartis, is currently underway in Greater Manchester to assess the feasibility of delivering inclisiran within a primary care setting, aiming to recruit 900 patients across approximately 20 practices. The results of this trial are due to be available in 2022.5

RCGP and BMA position

Cardiovascular disease prevention is a high priority for GPs and integral to the NHS Long Term Plan.6 Whilst the RCGP and BMA fully support innovation and promoting population health approaches to care, we have ongoing questions regarding the roll out of this novel medication. Our priority is to ensure the best possible care for patients.

Our main questions and concerns centre on the fact this is a black triangle drug7 being proactively rolled out directly to primary care, and in particular:

  • The lack of long-term data on cardiovascular outcomes - relevant studies are not due to be available until 2026
  • The lack of long-term safety data and as yet potential unknown long term side effects and interactions of the medication
  • The possible additional capacity or resources which may be required in primary care to deliver this novel drug at a time of unprecedented demand and shortages in workforce
  • The request for the drug to be given green status prior to regional medical optimisation committee review

We have not been reassured by the answered provided by NHSE/I and therefore the RCGP encourage practices to continue to treat patients with high cholesterol following lipid guidelines focussing on all available options starting with lifestyle changes and statins, escalating patients to high intensity statins and ezetimibe where appropriate and if considering injectable therapies consider all options, being aware that if you initiate inclisiran in primary care, or continue to prescribe the medication following initiation elsewhere as the decision maker, you take full responsibility for the prescribing.

Since inclisiran is a black triangle drug7, if you do decide to prescribe it before the long-term outcome and safety data is realised, please ensure you:

  • Undertake shared decision making with your patients, ensuring a full and detailed informed consent is taken, documenting the lack of long-term evidence and unknown long term safety profile of this new and novel medication,
  • Encourage your patients to report all side effects to you, however minor, ensuring you fill in a MHRA “yellow card” when they are reported to you and
  • Report any potential drug interactions or concerns of your own at the earliest opportunity

This approach will enable any as yet unknown issues to be identified early and help inform how the medication can be used in the future, alongside the trial data that are expected to publish in 2026.

Next steps

The RCGP and BMA will communicate an update to our members once we have further details of the long term trail data in 2026.

References

  1. NICE guidance on inclisiran
  2. Leqvio 284 mg solution for injection in pre filled syringe
  3. Inclisiran for treating primary hypercholesterolaemia or mixed dyslipidaemia (external PDF)
  4. Inclisiran leqvio
  5. Study in Primary Care Evaluating Inclisiran Delivery Implementation + Enhanced Support (SPIRIT)
  6. Cardiovascular disease
  7. List of medicinal products under additional monitoring (external PDF)