Sanofi and Regeneron Pharmaceuticals have announced the data from two Phase 2 primary hypercholesterolemia trials with SAR236553/REGN727, designed to lower low-density lipoprotein (LDL) cholesterol in patients.
SAR236553/REGN727 is a high-affinity, subcutaneously administered, fully-human monoclonal antibody directed against proprotein convertase subtilisin/kexin type 9 (PCSK9), a determinant of circulating LDL-cholesterol levels in the blood.
Study 11565 was a randomised double-blind multi-dose placebo-controlled trial that administered 183 patients with one of five different dose regimens of SAR236553/REGN727 - either 50mg, 100mg, or 150mg Q2W, or 200mg or 300mg Q4W alternating with placebo at two weeks - plus continued atorvastatin or placebo.
In the randomised double-blind multi-dose placebo-controlled Study 11566, 92 patients were randomised to either titration from atorvastatin 10mg to atorvastatin 80mg plus SAR236553/REGN727 150mg Q2W, titration from atorvastatin 10mg to atorvastatin 80mg plus placebo, or continued atorvastatin 10mg plus SAR236553/REGN727 150mg Q2W.
The primary endpoint of Study 11565 was the change in LDL-cholesterol from baseline over the 12-week study period, while in Study 11566 it was the change in LDL-cholesterol from baseline over the eight-week study period.
Both trials showed that treatment with SAR236553/REGN727 over eight to 12 weeks considerably reduced mean low-density lipoprotein-cholesterol by 40% to 72% in patients with elevated LDL-C on a stable dose of statins.
National Clinical Research president and CEO and principal investigator of the study James McKenney said the trial results suggest that SAR236553/REGN727 may enable patients for whom statins are insufficient to further reduce LDL-C.
Sanofi global research and development president Elias Zerhouni said genetic data has shown that patients with natural loss-of-function mutations in PCSK9 have lower LDL-C and a lower risk of coronary heart disease.
"Based on this finding and the results of our Phase 2 trials, Sanofi and Regeneron plan to initiate the SAR236553/REGN727 Phase 3 program in the second quarter," Zerhouni added.