Date: 2012-11-06
Type of information: Publication of results in a medical journal
phase: 2
Announcement: publication of Phase 2 Results with LDL Cholesterol-Lowering PCSK9 Antibody in the New England Journal of Medicine
Company: Sanofi (France) Regeneron Pharmaceuticals (USA - NY)
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 heterozygous familial hypercholesterolemia (heFH)
patients with primary hypercholesterolemia with elevated LDL-C
Therapeutic area: Cardiovascular diseases - Genetic diseases - Rare diseases
Country:
Trial
details: This study was part of the Phase 2 program of SAR236553/REGN727, an investigational, subcutaneously administered, fully-human antibody targeting PCSK9 (proprotein convertase subtilisin/kexin type 9) that is currently being studied in the ODYSSEY Phase 3 trials for the lowering of low-density lipoprotein cholesterol (LDL-C).
The study enrolled patients with primary hypercholesterolemia with elevated LDL-C (greater than or equal to 100 mg/dL) who were on a stable low dose of atorvastatin (10 mg). The primary objective of the study was to compare the effect on LDL-C lowering of switching to a high dose of atorvastatin alone (80 mg) versus a high dose of atorvastatin combined with SAR236553/REGN727 administered in a 1ml injection every two weeks.
SAR236553/REGN727 has been studied in three Phase 2 clinical studies: Two dose ranging studies in patients with hypercholesterolemia; one with 183-patients, and another with 92-patients, and one study of 77 patients with heterozygous familial hypercholesterolemia (heFH).
Latest
news: Sanofi and Regeneron Pharmaceuticals have announced that results from a Phase 2 trial of SAR236553/REGN727 in patients with primary hypercholesterolemia were published in the October 31, 2012 issue of the New England Journal of Medicine.
Patients who received SAR236553/REGN727 administered in a 1ml injection every two weeks plus atorvastatin 80 mg achieved a mean reduction of 73% in LDL-C, compared to a mean reduction of 17% for patients who switched to atorvastatin 80 mg alone (p < 0.001) after eight weeks. Ninety percent (90%) of patients achieved a pre-specified level of 70mg/dL compared to 17.2% for patients who switched to atorvastatin 80 mg alone (p < 0.001).
The study also included a third arm in which SAR236553/REGN727 150mg administered in a 1ml injection every two weeks was added to the stable 10 mg of atorvastatin. Ninety-six percent (96.6%) of patients achieved the pre-specified goal of 70mg/dL in this treatment group.
In this trial, the most common adverse events (AE) reported in patients treated with SAR236553/REGN727 plus atorvastatin were headache, dizziness, and diarrhea. There was one serious AE in the SAR236553/REGN727 plus atorvastatin 80 mg group (dehydration) that was deemed not to be treatment-related.
