Date: 2012-05-26
Type of information: Publication of results in a medical journal
phase: 2
Announcement: online publication of phase 2 results in The Lancet
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: heterozygous familial hypercholesterolemia
Therapeutic area: Cardiovascular diseases - Genetic diseases - Rare diseases
Country:
Trial
details: 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.
Latest
news: Sanofi and Regeneron Pharmaceuticals have announced additional positive results from a Phase 2 trial of SAR236553/REGN727 (Study 1003, NTC01266876) in patients with heterozygous familial hypercholesterolemia (heFH). The results from this study were published online in The Lancet and also presented at a late-breaking oral session at the 80th European Atherosclerosis Society Congress (EAS) in Milan, Italy. There were no serious adverse events (SAE) on active treatment, while a single SAE was recorded for a patient in the placebo group. There were no elevations in liver function tests (LFT) >3 times the upper limit of normal (ULN) and no cases of elevated creatinine kinase (CK) were reported. The most common adverse event reported was injection-site reaction. Sanofi and Regeneron also announced 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.
The trial randomized 77 patients with heFH whose LDL-cholesterol (LDL-C) levels remained uncontrolled on statin therapy with or without ezetimibe. Across the four different dosing regimens tested, patients receiving SAR236553 / REGN727 for 12 weeks achieved a mean LDL-C reduction from baseline of 28.9% to 67.9%, compared to 10.7% in patients receiving placebo (p
