Sanofi and Regeneron announced the results of 2 Phase 3b/4 trials at the 77th Scientific Sessions of the American Diabetes Association in San Diego, CA. The 2 trials, ODYSSEY DM-INSULIN and ODYSSEY DM-DYSLIPIDEMIA,1,2 studied the effects of Praluent® (alirocumab, Sanofi US and Regeneron Pharmaceuticals, Inc.) as supplement to maximally tolerated doses (MTD) of statins in diabetic patients. Both studies projected positive results in the reduction of cholesterol levels, as well as helping patients reach their lipid goals.
Previously, results from the ODYSSEY LONG TERM study (Long-term Safety and Tolerability of Alirocumab [SAR236553/REGN727] Versus Placebo on Top of Lipid-Modifying Therapy in High Cardiovascular Risk Patients with Hypercholestoerolemia; ClinicalTrials.gov identifier: NCT01507831) showed a 60% reduction in LDL-C from baseline to week 24 in 545 patients with diabetes treated with Praluent 150 mg plus MTD statins.
In the ODYSSEY DM-INSULIN trial (Efficacy and Safety of Alirocumab Versus Placebo on Top of Maximally Tolerated Lipid Lowering Therapy in Patients With Hypercholesterolemia Who Have Type 1 or Type 2 Diabetes and Are Treated With Insulin; ClinicalTrials.gov identifier: NCT02585778), patients were randomized in a double-blind, placebo-controlled, parallel-group multicenter study to Praluent 75 mg every 2 weeks or placebo in addition to MTD statins. Patients had either type 1 (n=76) or type 2 (n=441) diabetes, were on insulin therapy, and had hypercholesterolemia with MTD statins and high CV risk. The dose was adjusted at week 12 to 150 mg every 2 weeks if LDL-C ≥70 mg/dL at week 8.
Praluent achieved its primary endpoint by decreasing LDL-C from baseline to week 24 by 48.2%, compared to a 0.8% increase in the placebo arm (P <.0001). Additionally, 80% of patients in the Praluent arm reached their LDL-C goals with Praluent 75 mg every 2 weeks.
In the ODYSSEY DM-DYSLIPIDEMIA trial (Efficacy and Safety of Alirocumab Versus Usual Care on Top of Maximally Tolerated Statin Therapy in Patients With Type 2 Diabetes and Mixed Dyslipidemia; ClinicalTrials.gov identifier: NCT02642159), patients with type 2 diabetes and mixed dyslipidemia (n=413) were randomized in an open-label, parallel-group, multicenter, multinational study to Praluent 75 mg every 2 weeks or standard care in addition to MTD statins. Patients were at high CV risk and were inadequately controlled with MTD statins. Praluent was adjusted at week 12 to 150mg every 2 weeks if non-HDL-C ≥100 mg/dL at week 8.
The primary endpoint of the ODYSSEY DM-DYSLIPIDEMIA study was the percent change non-HDL-C from baseline to week 24. Results showed that Praluent every 2 weeks was superior to usual care in decreasing non-HDL-C (37.3% vs 4.7%; P <.0001). Sixty-four percent of patients reached their lipid goals with the addition of Praluent therapy. Praluent significantly reduced LDL-C levels by 43.3%, compared to usual care which increased LDL-C by 0.3%.
In both trials, Praluent demonstrated improvement in overall lipid profile in patients and did not negatively impact glycemic control, as measurements of fasting blood glucose, A1C, and diabetes therapy remained stable throughout the study.
Overall, given its tolerability and benefit in improving lipid profiles and achieving lipid goals, Praluent showed potential as adjunct therapy in patients with diabetes and hypercholesterolemia.
Praluent, a PCSK9 inhibitor, targets LDL receptors (LDLR) on hepatocytes. By interfering with the binding between PCSK9 and LDLR, Praluent increases the availability of LDLR to clear circulating LDL-C, thus decreasing LDL-C levels. Currently, Praluent is approved as adjunctive therapy to diet and MTD statin therapy for the treatment of heterozygous familial hypercholesterolemia or clinical ACVD who require additional reduction in LDL-C.
Praluent is supplied as cartons of 1 or 2 pre-filled pens, or 1 or 2 pre-filled syringes, designed to deliver 1 mL of 75 mg/mL or 150 mg/mL solution.
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- Leiter LA. Alirocumab and insulin-treated diabetes — insights from the ODYSSEY DM-INSULIN study. Presented at: American Diabetes Association 77th Scientific Sessions; June 9-13, 2017; San Diego, CA. Presentation 1-AC-SY12
- Henry RR. Alirocumab vs usual care in diabetes with mixed dyslipidemia — ODYSSEY DM-DYSLIPIDEMIA study. Presented at: American Diabetes Association 77th Scientific Sessions; June 9-13, 2017; San Diego, CA. Presentation 1-AC-SY12
This article originally appeared on MPR