Sanofi and Regeneron Pharmaceuticals, Inc. have announced that the ODYSSEY OUTCOMES trial, a phase 3 cardiovascular outcomes trial (CVOT) with SAR236553/REGN727 is now recruiting patients.

SAR236553/REGN727 is an investigational subcutaneously administered, fully-human antibody that is being evaluated for its impact on lowering low-density lipoprotein cholesterol (LDL-C) by targeting PCSK9 (proprotein convertase subtilisin/kexin type 9).

The ODYSSEY OUTCOMES trial will enroll approximately 18,000 patients, who recently suffered an acute coronary syndrome (ACS), from 49 countries across six continents. With the start of this study, eleven trials are now recruiting in the companies’ global anti-PCSK9 phase 3 programme.

“Despite widespread use of statin therapy, many patients at risk do not reach recommended targets for LDL. Even among those who do reach targets, further LDL lowering may further reduce the risks of coronary heart disease (CHD) death, myocardial infarction (MI) and stroke,” said Ph. Gabriel Steg M.D., Professor of Cardiology at the Hôpital Bichat-Claude Bernard in Paris, France, and co-Chair of the ODYSSEY OUTCOMES Steering Committee. “The ODYSSEY cardiovascular (CV) outcomes trial will test the efficacy and safety of SAR236553/REGN727 added to maximal doses of statins in reducing cardiovascular morbidity and mortality in patients with recent ACS, a population at high risk of CV events despite best contemporary therapy."

ODYSSEY OUTCOMES is a double-blind, randomized, placebo-controlled, multi-national study. The primary objective of the study is to evaluate the effect of our anti-PCSK9 on the incidence of cardiovascular events in patients who have experienced an ACS and are not at LDL-C goal. Patients will receive either a 1-milliliter (mL) injection of 75 milligrams (mg) of SAR236553/REGN727 or placebo every two weeks, in addition to individually optimized lipid-lowering therapy. If patients do not reach a predetermined LDL-C goal with the 75 mg dose they will be up-titrated to a dose of 150 mg, also delivered as a 1 mL injection. The primary endpoint is a composite of coronary heart disease (CHD) death, non-fatal MI, fatal and non-fatal ischemic stroke, and unstable angina requiring hospitalization. ODYSSEY OUTCOMES is being conducted under a Special Protocol Assessment (SPA) agreed upon with the US Food and Drug Administration (FDA).

The broad phase 3 ODYSSEY programme is underway and will be conducted across more than 2,000 study centres across the United States, Canada, Western and Eastern Europe, South America, Australia and Asia.

Based on the cumulative efficacy and safety data from the SAR236553/REGN727 phase 1 and phase 2 clinical studies, 75 mg and 150 mg Q2W doses were chosen to be tested in the Phase 3 program. The selection of these doses was also supported by information from current lipid treatment guidelines and data from large, completed CV event trials that have demonstrated a correlation between the degree of LDL-C lowering and the resultant lowered risk for CV events.

PCSK9 is known to be a determinant of circulating LDL-C levels, as it binds to LDL receptors resulting in their degradation so that fewer are available on liver cells to remove excess LDL-C from the blood. Moreover, traditional LDL-lowering therapies such as statins actually stimulate the production of PCSK9, which limits their own ability to lower LDL-C. Blocking the PCSK9 pathway is therefore a potentially novel mechanism for lowering LDL-C.

SAR236553/REGN727, created using Regeneron’s VelocImmune® technology, is a fully human monoclonal antibody targeting PCSK9, administered via subcutaneous injection. By inhibiting PCSK9, a determinant of circulating LDL-C levels in the blood, SAR236553/REGN727 has been shown in pre-clinical studies to increase the number of LDL receptors which can clear circulating LDL-C from the bloodstream.