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ORION-8 results showed the change in LDL-C from baseline in the 3-year open-label extension was similar to the change observed during 18 months of placebo-controlled comparison.
New results from the ORION-8 trial indicate the long-term benefit, safety, and tolerability of inclisiran in patients with high cardiovascular risk and elevated low-density lipoprotein-cholesterol (LDL-C).
Presented at the European Society of Cardiology 2023 Congress, results from ORION-8 show the change from baseline in LDL-C over 3 additional years of open-label extension was similar to changes seen in the 18 months of placebo-controlled comparison.
“What we are seeing is that with a therapy like inclisiran, which can be given on days 1 and 90, and then every 6 months thereafter, you can achieve extremely low LDL levels and get your patient to their target threshold,” said R.Scott Wright, MD, a professor of medicine and cardiology at Mayo Clinic, in an interview with HCPLive. “We were quite pleased to see that the great majority of patients could be at goal with the use of inclisiran plus a statin or insclisiran plus ezetimibe.”
Pooled analyses of the phase 3 ORION-9, ORION-10, and ORION-11 placebo-controlled trials detailed the effect of inclisiran, a siRNA therapeutic targeting proprotein convertase subtilisin/kexin type 9, in more than 3500 patients, lowering LDL-C by ~52% over an 18-month period, with a good safety profile. The ORION-3 trial of nearly 400 patients showed lowering with twice-yearly inclisiran was maintained over a 4-year period.
Patients from these trials were invited to participate in the ORION-8 extension trial to further assess the long-term efficacy, safety, and tolerability of inclisiran. Those enrolled in ORION-8 received an open-label subcutaneous dose of 300 mg inclisiran sodium every 6 months up to Day 1080. A total of 3274 patients were included in ORION-8; 2446 (74.7%) completed the trial to Day 1080.
At baseline, patients had a mean age of 65 years and 56.5% were aged ≥65 years. The mean baseline LDL-C was 113.0 mgdL and 82.7% of patients had atherosclerotic cardiovascular disease. The prespecified LDL-C targets were listed as either <70 mg/dL in patients with ASCVD or <100 mg/dL in patients with ASCVD risk equivalent
Overall, the mean duration and total inclisiran exposure in ORION-8 were 2.6 years and 8538.84 patient years, respectively. The number of patients with at least one new or changed background lipid-modifying therapy after the study began was 360 patients (11.0%).
Upon analysis, the proportion of patients achieving the prespecified LDL-C targets with inclisiran treatment was 78.4% (95% CI, 76.8 - 80.0). In addition, the mean percent change in LDL-C from baseline at the end-of-study visit was a reduction of 49.4% (95% CI, -50.4 to -48.3).
Investigators also indicate the proportion of patients achieving the prespecified LDL-C targets and the mean percent change in LDL-C from baseline at the end-of-study visit was 78.4% (95% CI, 76.8 - 80.0) and –49.4% (95% CI, –50.4 to –48.3), respectively.
The number of patients achieving LDL-C targets at the end-of-study visit was similar between patients with ASCVD (79.4%; 95% CI, 77.7 - 81.1) and ASCVD-risk equivalent (74.3%; 95% CI, 70.4 - 78.0). No new safety signals were identified by investigators.
For greater insight into findings from the ORION-8 trial, watch the full interview with Dr. Wright.
Wright discusses how the pooled patient population might inform real-world use, the recent inclisiran label update from the US Food and Drug Administration (FDA), and the importance of cardiovascular risk reduction through optimal lipid management in diabetes.
Relevant disclosures for Dr. Wright include Boehringer Ingelheim Pharmaceuticals, Inc.