Sanofi and Regeneron Pharmaceuticals have reported promising data from two phase II trials with SAR236553/REGN727—an investigational, high-affinity, subcutaneously administered, fully-human antibody targeting PCSK9 (proprotein convertase subtilisin/kexin type 9).
The data showed that treatment with SAR236553/REGN727 over 8 to 12 weeks significantly reduced mean low-density lipoprotein-cholesterol (LDL-C, or "bad" cholesterol) by 40-72% in patients with elevated LDL-C on stable dose of statins.
"Many patients are not able to lower their LDL-C sufficiently by diet and medication despite the availability of statins. As guidelines are evolving, there is a real need for additional lipid-lowering medications," said Dr. James McKenney, president and CEO of National Clinical Research and principal investigator of the study. "These trial results suggest that SAR236553/REGN727 may enable patients for whom statins are insufficient to further reduce LDL-C."
The phase II dose-finding clinical trial enrolled 183 patients with elevated LDL-C (greater than or equal to 100mg/dL) despite being on a stable dose of atorvastatin. The objective of the study was to evaluate the effect of adding SAR236553/REGN727 to existing statin therapy. Across the five different dose regimens tested, patients receiving SAR236553/REGN727 for 12 weeks achieved and sustained a mean LDL-C reduction from baseline of 40% to 72%, compared to 5% in patients receiving placebo (p<0.0001). Patients in the study were followed for a total of 20 weeks for safety.
The most common adverse events (AEs) with SAR236553/REGN727 were injection site reactions. Serious AEs occurred in one patient receiving placebo and three patients in the active treatment arms, including a patient on active treatment who experienced a skin rash diagnosed as leukocytoclastic vasculitis. Six patients, all on active treatment, prematurely discontinued therapy due to AEs.
"Genetic data have shown that patients with natural loss-of-function mutations in PCSK9 have significantly lower LDL-C and a lower risk of coronary heart disease," said Dr. Elias Zerhouni, president, global R&D, Sanofi. "Based on this finding and the results of our phase II trials, Sanofi and Regeneron plan to initiate the SAR236553/REGN727 phase III program in the second quarter."
A long-term safety and tolerability study of SAR236553/REGN727 (NCT01507831) is ongoing in patients with hypercholesterolemia who are not adequately controlled with their current lipid-modifying therapy.