Date: 2016-11-17
Type of information: DSMB assessment
phase: 3
Announcement: completion of the trial
Company: Sanofi (France) Regeneron Pharmaceuticals (USA - NY)
Product: Praluent® (alirocumab - SAR236553/REGN727)
Action
mechanism:
Disease: acute coronary syndrome
Therapeutic area: Cardiovascular diseases - Genetic diseases - Rare diseases
Country: Argentina, Australia, Austria, Belgium, Bosnia and Herzegovina, Brazil, Bulgaria, Canada, Chile, China, Colombia, Croatia, Czech Republic, Denmark, Estonia, Finland, France, Georgia, Germany, Greece, Guatemala, Hong Kong, Hungary, India, Israel, Italy, Japan, Republic of Korea, Latvia, Lithuania, Macedonia, The Former Yugoslav Republic of, Malaysia, Mexico, Netherlands, New Zealand, Norway, Peru, Philippines, Poland, Portugal, Romania, Russian Federation, Serbia, Singapore, Slovakia, Slovenia, South Africa, Spain, Sri Lanka, Sweden, Switzerland, Taiwan, Thailand, Turkey, Ukraine, UK, USA
Trial
details: The ODYSSEY program will enroll more than 23,000 patients. This includes over ten clinical trials evaluating the effect of SAR236553/REGN727 on the lowering of LDL cholesterol and an 18,000 patient cardiovascular outcomes (e.g., heart attacks, stroke) study. LDL-C is expected to be the primary efficacy endpoint for regulatory filings. The studies will be conducted in clinical centers around the world including USA, Canada, Western and Eastern Europe, South America, Australia and Asia.
The Phase 3 ODYSSEY program will include over ten clinical trials designed to test the efficacy and long-term safety of SAR236553/REGN727 both as monotherapy, and in combination with other lipid-lowering agents. ODYSSEY will enroll several patient populations including patients with heFH who are inadequately controlled by current lipid-modifying therapy, and high cardiovascular risk patients with primary hypercholesterolemia. The primary efficacy parameter will be LDL-C; however, multiple lipid parameters will be evaluated.
The Phase 3 ODYSSEY program will include the following studies:
* ODYSSEY FH I, FH2 and HIGH FH: The primary objective of these three studies is to demonstrate the efficacy and safety of SAR236553/REGN727 as add-on therapy in patients with heFH who are not adequately controlled with their lipid-modifying therapy.
* ODYSSEY COMBO I and COMBO II: The primary objective of these two studies is to demonstrate the safety and efficacy of SAR236553/REGN727 as an add-on therapy in patients with primary hypercholesterolemia at high cardiovascular risk who are not adequately controlled with their lipid-modifying therapy.
* ODYSSEY MONO: (N=103) was a randomized, double-blind, active-controlled, parallel-group study to evaluate the efficacy and safety of alirocumab over 24 weeks in patients with primary hypercholesterolemia and moderate cardiovascular risk. Patients in the trial were randomized to receive monotherapy with either ezetimibe 10 mg, an alternative to statin therapy, or alirocumab. Alirocumab was self-administered initially at its low dose of 75 mg every two weeks, and was up-titrated at week 12 to 150 mg if the LDL-C measurement at week 8 was above 70 mg/dL. The majority of alirocumab patients in the trial remained on the initial low dose of alirocumab because they achieved LDL-C below 70 mg/dL at week 8. Alirocumab was self-administered subcutaneously using a single 1 milliliter (mL) auto-injector.
* ODYSSEY ALTERNATIVE: The primary objective of this study is to demonstrate the safety and efficacy of SAR236553/REGN727 in comparison with ezetimibe in patients with primary hypercholesterolemia who are unable to tolerate statins.
* ODYSSEY OPTIONS I and OPTIONS II: The primary objective of these studies is to evaluate the safety and efficacy of SAR236553/REGN727 as an add-on therapy in patients with primary hypercholesterolemia at high cardiovascular risk or with heFH who are not adequately controlled on statins, in comparison to several second line lipid lowering strategies.
* ODYSSEY LONG TERM: The primary objective of this study is to evaluate the long-term safety and tolerability of SAR236553/REGN727 in patients with hypercholesterolemia at high cardiovascular risk or patients with heFH inadequately controlled with their current lipidmodifying therapy.
In addition, the ODYSSEY program will also include ODYSSEY OUTCOMES, a Phase 3 cardiovascular outcomes trial which will enroll about 18,000 patients and evaluate the effect of SAR236553/REGN727 on the occurrence of cardiovascular events. (NCT01663402)
Latest news: • On November 17, 2016, Sanofi and Regeneron Pharmaceuticals announced that the ongoing Praluent® (alirocumab) ODYSSEY OUTCOMES trial will continue as planned, based on the recommendation of an independent Data Monitoring Committee (DMC) after it completed a second pre-specified interim analysis. The DMC will continue to monitor the ongoing safety and efficacy of Praluent® as planned. • On November 24, 2015, Sanofi and Regeneron Pharmaceuticals announced that the companies have completed enrollment in the global Phase 3 ODYSSEY OUTCOMES trial, which is prospectively evaluating the potential cardiovascular (CV) benefits of Praluent® (alirocumab) Injection after an acute coronary syndrome (ACS). The 18,000-patient ODYSSEY OUTCOMES trial is expected to be completed in 2017. ODYSSEY OUTCOMES is designed to determine whether the addition of Praluent to intensive statin therapy reduces major adverse cardiac events among patients who had previously experienced an ACS, such as a heart attack or unstable angina. The primary endpoint evaluates the time to first occurrence of coronary heart disease death, acute myocardial infarction, hospitalization for unstable angina, or fatal and non-fatal ischemic stroke. Patients with recent ACS were selected as the study population because they face a higher risk of recurrent events than patients with stable cardiovascular disease.
