Date: 2011-11-10
Type of information:
phase: 2
Announcement: results
Company: Sanofi (France) Regeneron Pharmaceuticals (USA)
Product: REGN727/SAR236553
Action mechanism: REGN727/SAR236553 is a fully-human monoclonal antibody directed against PCSK9 (proprotein convertase subtilisin/kexin type 9), administered via subcutaneous injection. 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:
elevated low-density lipoprotein cholesterol
Therapeutic area: Cardiovascular diseases - Metabolic diseases
Country:
Trial
details: The REGN727/SAR236553 Phase 2 program consists of three Phase 2 clinical trials. These are: - A randomized, double-blind, multi-dose, placebo-controlled, 75-patient trial in patients with heterozygous familial hypercholesterolemia (heFH). In this trial, patients must meet the World Health Organization criteria for heFH, be on a stable daily statin regimen for at least 6-weeks before entering the trial, and have serum LDL-C levels >/= 100mg/dL. Patients could be taking ezetimibe in addition to a daily statin. Patients were randomized to one of four different dose regimens of REGN727/SAR236553 or placebo. The primary endpoint of the study is the change in LDL-C from baseline over the 12-week study period. Patients will be followed for a total of 20 weeks for safety.
- A randomized, double-blind, single-dose, placebo-controlled, 90-patient trial in combination with atorvastatin in patients with primary hypercholesterolemia. In this trial, patients on a stable dose of atorvastatin 10mg for at least 6-weeks with LDL-C levels >/= 100mg/dL or who had LDL-C levels >/= 100mg/dL after a run-in period on atorvastatin 10mg, were randomized to either (a) titration from atorvastatin 10mg to atorvastatin 80mg plus REGN727/SAR236553, (b) titration from atorvastatin 10mg to atorvastatin 80mg plus placebo, or (c) continued atorvastatin 10mg plus REGN727/SAR236553. The primary endpoint of the study is the change in LDL-C from baseline over the 8-week study period. Patients were followed for a total of 16 weeks for safety.
- A randomized, double-blind, multi-dose, placebo-controlled, 180-patient trial in combination with atorvastatin in patients with primary hypercholesterolemia and on stable doses of atorvastatin. In this trial, patients on a stable dose of atorvastatin 10mg, atorvastatin 20mg, or atorvastatin 40mg for at least 6-weeks with LDL-C levels >/= 100mg/dL or who had LDL-C levels >/= 100mg/dL after a run-in period on atorvastatin 10mg, atorvastatin 20mg, or atorvastatin 40mg were randomized to one of five different dose regimens of REGN727/SAR236553 plus continued atorvastatin or placebo plus continued atorvastatin. The primary endpoint of the study is the change in LDL-C from baseline over the 12-week study period. Patients will be followed for a total of 20 weeks for safety.
Latest
news: Sanofi and Regeneron Pharmaceuticals have announced positive preliminary results from the Phase 2 study program in which patients with elevated low-density lipoprotein cholesterol (LDL-C) were treated with REGN727/SAR236553. Another Phase 2 trial studied patients with primary hypercholesterolemia with elevated cholesterol (LDL-C>/= 100mg/dL) who were on a stable low dose of atorvastatin (10 mg). The primary objective of the study was to compare the effect of switching to a high dose of atorvastatin alone (80mg) versus a high dose of atorvastatin combined with REGN727/SAR236553. In the primary endpoint of the study, after eight weeks of treatment, patients who received REGN727/SAR236553 plus atorvastatin 80mg achieved a greater than 65% reduction in mean LDL-C compared to a mean reduction of 17% for atorvastatin 80mg only (p<0.001). The study also included a third arm in which REGN727/SAR236553 was added to the stable low dose of atorvastatin and the patients achieved a greater than 65% reduction in mean LDL-C. Patients in the study were followed for a total of 16 weeks for safety. In this trial, REGN727/SAR236553 was generally well tolerated over 16 weeks. There was one serious adverse event of dehydration in the REGN727/SAR236553 + atorvastatin 80mg group that was deemed not treatment related. One patient in the REGN727/SAR236553 + atorvastatin 80mg group with mildly elevated AST prior to randomization (>ULN and 3ULN and
One Phase 2 trial studied patients with heterozygous familial hypercholesterolemia (heFH) with elevated cholesterol (LDL-C>/=100mg/dL) despite lipid lowering therapy (statins with or without ezetemibe). The objective of the study was to compare the effect of adding REGN727/ SAR236553 to the existing lipid lowering therapy in heFH patients. In the primary efficacy analysis of the study, after 12 weeks of treatment, patients who received different dosing regimens of REGN727/SAR236553 achieved mean LDL-C reductions from baseline ranging from approximately 30% to greater than 65% depending on the dosing regimen of REGN727/SAR236553 compared to a mean reduction of 10% with placebo (p<0.05 for all dose groups). Patients in the study are being followed for a total of 20 weeks for safety.
In this trial, REGN727/SAR236553 was generally well tolerated over 12 weeks. There were no elevations in LFTs >3 times the upper limit of normal (ULN) and no cases of elevated CPK reported. The most common adverse event was injection site reaction. There were no serious adverse events on active treatment. Full safety data from the 8-week post-treatment monitoring period will be presented at a future medical congress upon final analysis.
