Positive Phase II Results Reported for Sanofi/Regeneron Pharmaceuticals Cholesterol Drug
Sanofi and Regeneron Pharmaceuticals, Inc. recently announced positive preliminary results from the Phase II study program in which patients with elevated low-density lipoprotein cholesterol (LDL-C) were treated with REGN727/SAR236553.
REGN727/SAR236553 is a novel, high-affinity, subcutaneously administered, fully human antibody targeting PCSK9 (proprotein convertase subtilisin/kexin type 9). Blocking the PCSK9 pathway is a novel mechanism for lowering LDL-C, the leading known risk factor for coronary artery disease.
One Phase II trial studied patients with heterozygous familial hypercholesterolemia (heFH) with elevated cholesterol (LDL-C>/=100 mg/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.
Another Phase II trial studied patients with primary hypercholesterolemia with elevated cholesterol (LDL-C>/= 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 of switching to a high dose of atorvastatin alone (80 mg) versus a high dose of atorvastatin combined with REGN727/SAR236553. In the primary endpoint of the study, after 8 weeks of treatment, patients who received REGN727/SAR236553 plus atorvastatin 80 mg achieved a greater than 65% reduction in mean LDL-C compared to a mean reduction of 17% for atorvastatin 80 mg 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 80 mg group that was deemed not treatment related. One patient in the REGN727/SAR236553 + atorvastatin 80-mg group with mildly elevated AST prior to randomization (>ULN and </= 3ULN) experienced an elevation of AST>3ULN and </=5ULN, and one patient discontinued therapy due to a hypersensitivity reaction (rash). A third study of this Phase II program is still ongoing.
“The preliminary Phase II results with our anti-PCSK9 antibody are very encouraging,” said Elias Zerhouni, President, Global Research & Development, Sanofi. “We look forward to analyzing and presenting the complete data set and remain committed to advancing this program into Phase III development as soon as possible.”
“Despite the availability of statins, elevated cholesterol and coronary artery disease remain a leading cause of morbidity and mortality in the
More detailed data from these Phase II trials, as well as from the third ongoing Phase II trial, will be submitted for presentation at an upcoming scientific conference.
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