Date: 2012-07-20
Type of information:
phase: 3
Announcement: initiation of patient enrollment
Company: Sanofi (France) Regeneron Pharmaceuticals (USA)
Product: SAR236553/REGN727
Action mechanism: SAR236553 / REGN727 is a subcutaneously administered, fully-human antibody targeting PCSK9 (proprotein convertase subtilisin/kexin type 9) in clinical development. By inhibiting PCSK9, a determinant of circulating LDL-cholesterol levels in the blood, REGN727 increases the number of free LDL receptors which can bind to circulating LDL and clear it from the bloodstream. REGN727 was created using Regeneron's pioneering VelocImmune® technology and is being developed by Regeneron in collaboration with Sanofi.
Disease: - patients with heFH who are inadequately controlled by current lipid-modifying therapy
- high cardiovascular risk patients with primary hypercholesterolemia
Therapeutic area: Cardiovascular diseases - Metabolic diseases
Country: USA, Canada, Western and Eastern Europe, South America, Australia and Asia
Trial
details: The ODYSSEY program will enroll more than 22,000 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: The primary objective of this study is to demonstrate the safety and efficacy of SAR236553/REGN727 as monotherapy in comparison with ezetimibe in patients with primary hypercholesterolemia.
* 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.
Latest
news: Sanofi and Regeneron Pharmaceuticals have announced that several trials within ODYSSEY, the Phase 3 clinical program of SAR236553/REGN727, have initiated patient enrollment. This comprehensive Phase 3 program will test the safety and efficacy of SAR236553/REGN727 administered as one single injection every two weeks in multiple treatment strategies and patient types, such as those who are at elevated cardiovascular risk, are unable to tolerate statin therapy, or have familial hypercholesterolemia.
In parallel, Sanofi announced the creation of a dedicated PCSK9 Development & Launch Unit. Jay Edelberg, M.D., Ph.D. has recently been appointed as Head of the Development & Launch Unit, reporting to Elias Zerhouni, President, Global R&D and Hanspeter Spek, President, Global Operations, Sanofi. The creation of a dedicated unit for this new PCSK9 inhibitor underscores Sanofi’s commitment to develop this potential first-in-class therapeutic agent.
SAR236553/REGN727 has been studied in three Phase 2 clinical studies: two in patients with primary hypercholesterolemia and one in patients with heterozygous familial hypercholesterolemia (heFH). In the primary hypercholesterolemia trials treatment with different dose regimens of SAR236553/REGN727 on top of statin therapy significantly reduced LDL-C from baseline by 40% to 72% over the 8 or 12-week treatment period.
A third Phase 2 study was in patients with HeFH whose LDL-C levels remained elevated despite statin therapy with or without ezetimibe. Across the four tested doses of SAR236553/REGN727 for up to 12 weeks, patients achieved a mean reduction in LDL-C from baseline of 28% to 68%.
In the Phase 2 program, injection site reactions were the most common adverse events with SAR236553/REGN727. Rare cases of hypersensitivity reaction were also reported. There were five serious adverse events (SAE) in the active treatment arms (1.8%, 5/275) and two SAEs in the placebo groups (2.6%, 2/77).
