ORION-4 Participant newsletter Issue 02, 2025

Inclisiran

Inclisiran is a treatment aimed at lowering bad cholesterol. Here’s some background information about inclisiran:

• How it works: Inclisiran is a special type of medicine that helps lower bad (LDL) cholesterol using a natural process in the body to stop the production of a protein called PCSK9. By doing this your liver is able to remove more bad cholesterol from your blood.
• Development: Earlier clinical trials, such as ORION-10 and ORION-11 have already shown that inclisiran substantially lowers bad cholesterol even in people who are already taking a statin (which is a medicine already used very commonly to lower cholesterol). The ORION-4 trial (with participants in the UK and USA) and the VICTORION-2P trial (with participants from 49 different countries) are testing the benefits and safety of inclisiran. •
• Approval: In October 2021, inclisiran was recommended by the National Institute for Health and Care Excellence (NICE) for some patients with heart and circulatory disease (cardiovascular disease) who have high levels of bad cholesterol. However, it is not yet being used very widely in the NHS. If the results from the ORION-4 trial show that inclisiran helps to protect against heart attacks and strokes then we hope that it will become widely available for patients.

Have you ever wondered what happens to your samples after you provide them? Our dedicated lab team works meticulously to analyse each sample.

• Sample Reception: Your samples are carefully logged and stored.
• Analysis: Our scientists use advanced techniques to study the samples.
• Results: The data collected helps us to understand the impact of inclisiran.

• Online Meetings: We recently held our first online meetings. These included updates on the trial from the Oxford team and Q&A sessions. We were delighted that about 1000 people were able to join us for these meetings.
• Site Visits: Over the last year, there have been eight meetings at different sites in the UK. This has allowed participants to meet members of the local research teams and staff from the central coordinating office in Oxford in person.

We have added some of the materials from the online meetings to the study website. 

As we approach the final stages of the ORION-4 trial, we encourage you to try to attend your remaining visits in person. Your continued participation is vital for the success of the study. The final visits for the study will start after Easter in 2026 and will continue throughout the summer. It is really helpful for ORION-4 if we can see everyone in person at your study clinic at the end of the study and also take a blood sample from as many participants as possible. Your study nurse will also want the chance to say a big thank you to you for taking part in the study and for helping us with this important research.

After your final follow-up, the trial team at the University of Oxford will take a few months to review and analyse data from all 16,124 participants. Once the results are ready, we will write to you and your GP with the study results, so that you can discuss with them what treatments you should be prescribed for your cholesterol in the future. At that time, you will have the option to learn which study treatment arm (inclisiran or placebo) you were assigned to during your participation in ORION-4.

If you have any questions or need assistance, please contact the ORION-4 coordinating centre.