Study of Alirocumab (REGN727/SAR236553) added-on to Rosuvastatin Versus Other Lipid Modifying Treatments (LMT) (ODYSSEY OPTIONS II)

Summary

To evaluate the reduction of low-density lipoprotein cholesterol (LDL-C) by alirocumab (REGN727/SAR236553) as an add-on therapy to other LMT in patients with hypercholesterolemia at high cardiovascular (CV) risk.

Timeline

Start

2012-11-30

Primary completion

2014-04-30

Completion

2014-05-31

Outcome

Missed primary endpoint

registry analysis (unspecified test); Rosuvastatin 40 mg vs Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg; p =0.0453; LS Mean Difference -20.3 (98.75% CI -45.8 to 5.1); Mixed Models Analysis; note: Threshold for significance ≤ 0.0125. NCT01730053 ↗

registry analysis (unspecified test); Ezetimibe 10 mg + Rosuvastatin 20 mg vs Alirocumab 75 mg/up to 150 mg + Rosuvastatin 20 mg; p =0.0136; LS Mean Difference -25.3 (98.75% CI -50.9 to 0.3); Mixed Models Analysis; note: Threshold for significance ≤ 0.0125. NCT01730053 ↗

Publications

• Mahmood T, Minnier J, Ito MK, Li QH, Koren A, Kam IW, Fazio S, Shapiro MD. Discordant responses of plasma low-density lipoprotein cholesterol and lipoprotein(a) to alirocumab: A pooled analysis from 10 ODYSSEY Phase 3 studies. Eur J Prev Cardiol. 2021 Jul 23;28(8):816-822. doi: 10.1177/2047487320915803. Epub 2020 Apr 10.
• Leiter LA, Tinahones FJ, Karalis DG, Bujas-Bobanovic M, Letierce A, Mandel J, Samuel R, Jones PH. Alirocumab safety in people with and without diabetes mellitus: pooled data from 14 ODYSSEY trials. Diabet Med. 2018 Dec;35(12):1742-1751. doi: 10.1111/dme.13817. Epub 2018 Oct 9.
• Ray KK, Ginsberg HN, Davidson MH, Pordy R, Bessac L, Minini P, Eckel RH, Cannon CP. Reductions in Atherogenic Lipids and Major Cardiovascular Events: A Pooled Analysis of 10 ODYSSEY Trials Comparing Alirocumab With Control. Circulation. 2016 Dec 13;134(24):1931-1943. doi: 10.1161/CIRCULATIONAHA.116.024604. Epub 2016 Oct 24.
• Farnier M, Jones P, Severance R, Averna M, Steinhagen-Thiessen E, Colhoun HM, Du Y, Hanotin C, Donahue S. Efficacy and safety of adding alirocumab to rosuvastatin versus adding ezetimibe or doubling the rosuvastatin dose in high cardiovascular-risk patients: The ODYSSEY OPTIONS II randomized trial. Atherosclerosis. 2016 Jan;244:138-46. doi: 10.1016/j.atherosclerosis.2015.11.010. Epub 2015 Nov 14.
• Robinson JG, Colhoun HM, Bays HE, Jones PH, Du Y, Hanotin C, Donahue S. Efficacy and safety of alirocumab as add-on therapy in high-cardiovascular-risk patients with hypercholesterolemia not adequately controlled with atorvastatin (20 or 40 mg) or rosuvastatin (10 or 20 mg): design and rationale of the ODYSSEY OPTIONS Studies. Clin Cardiol. 2014 Oct;37(10):597-604. doi: 10.1002/clc.22327. Epub 2014 Sep 30.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Alirocumab	Monoclonal antibody	75 mg	Subcutaneous
Subject	Alirocumab	Monoclonal antibody	150 mg	Subcutaneous
Comparator	Ezetimibe	Unknown	10 mg	Oral
Subject	Rosuvastatin	Small molecule	10 mg	Oral
Subject	Rosuvastatin	Small molecule	20 mg	Oral
Subject	Rosuvastatin	Small molecule	40 mg	Oral

Indications