"Heterozygous familial hypercholesterolemia is a common, serious, and often undiagnosed cause of early heart disease. There remains a high degree of unmet need in these patients as a large percentage are unable to reach optimal LDL-C goals despite being on maximal lipid-lowering therapy," said Evan A. Stein, M.D., Ph.D., Director of the Metabolic and Atherosclerosis Research Center in Cincinnati, Ohio, and Principal Investigator of the study. "These data suggest that SAR236553/REGN727 may provide a new option, on top of existing therapies, to lower LDL-cholesterol and finally reach LDL-C goals for these difficult-to-treat patients."
Sanofi and Regeneron also announced today that based on discussions with the U.S. and European regulatory authorities, they intend to initiate a global Phase 3 program with SAR236553/REGN727 in June. This will be the first Phase 3 program of an investigational drug targeting PCSK9.
"These data, along with recently presented data in patients with hypercholesterolemia, further support our belief that blocking PCSK9 with our antibody has the potential to offer a novel mechanism for lowering LDL-cholesterol in a broad range of patients," said George D. Yancopoulos, M.D., Ph.D., Chief Scientific Officer of Regeneron and President of Regeneron Laboratories. Dr. Elias Zerhouni, President, Global Research & Development, Sanofi, added: "Our global Phase 3 program will include patients with high unmet medical need, such as patients with familial hypercholesterolemia or with elevated cardiovascular risk who cannot reach their LDL-cholesterol goals with current standard therapies. The program reflects our excitement and commitment to develop this potential therapeutic option for these patients."
About PCSK9PCSK9 is known to be a determinant of circulating LDL-C levels, as it binds to LDL receptors resulting in their degradation so that fewer are available on liver cells to remove excess LDL-C from the blood. [ 4] Moreover, traditional LDL-lowering therapies such as statins actually stimulate the production of PCSK9, which limits their own ability to lower LDL-C. [ 5] Blocking the PCSK9 pathway is therefore a potentially novel mechanism for lowering LDL-C. About SAR236553/REGN727 and the Phase 2 Heterozygous Familial Hypercholesterolemia trial SAR236553/REGN727 is a fully human monoclonal antibody directed against PCSK9, administered via subcutaneous injection. By inhibiting PCSK9, a determinant of circulating LDL-C levels in the blood, SAR236553/REGN727 increases the number of free LDL receptors which can bind to circulating LDL-C and clear it from the bloodstream. SAR236553/REGN727 was created using Regeneron's VelocImmune ® technology. Study 1003 was a randomized, double-blind, placebo-controlled, dose-finding study in patients with heFH. The primary objective of the trial was to assess the efficacy of various subcutaneous doses and dosing regimens of SAR236553/REGN727 on LDL-C in patients with heFH. Seventy-seven patients were randomized to either placebo or one of four active dose regimens of 150 mg at four-week intervals (Q4W), 200 mg Q4W, 300 mg Q4W, or 150 mg at two-week intervals (Q2W). At baseline, all patients had LDL-C greater than or equal to 100 mg/dL (2.59 mmol/L) and were on stable daily statin therapy (the type and dosage of statin was at the discretion of the investigator) with or without ezetimibe, for at least six weeks prior to screening. The majority of patients, 77%, were taking a high intensity dose of a statin, and 71% were also taking ezetimibe 10 mg at the time of the screening visit and throughout the trial. Despite this aggressive therapy, the mean baseline LDL-C for all study participants was approximately 155 mg/dL (4 mmol/L). The primary endpoint of the study was the change in LDL-C from baseline over the 12-week study period. Patients were followed for a total of 20 weeks for safety.  About Heterozygous Familial Hypercholesterolemia